Patent application title: COMPOSITIONS, METHODS OF ADMINISTRATION AND USES FOR TRIVALENT DENGUE VIRUS FORMULATIONS
Inventors:
IPC8 Class: AA61K3912FI
USPC Class:
1 1
Class name:
Publication date: 2018-08-16
Patent application number: 20180228887
Abstract:
Embodiments of the present invention report compositions and methods for
vaccinating a subject using trivalent dengue virus vaccine compositions.
In some embodiments, more than one vaccine composition may be
administered to a subject in different anatomical locations in order to
induce a rapid response to at least three of four dengue virus serotypes.
In certain embodiments, administration of a trivalent dengue virus
vaccine composition can be combined with administration of a monovalent
dengue virus vaccine composition.Claims:
1-18 (canceled)
19. A trivalent dengue virus immunogenic composition comprising, at least one dengue-dengue chimera and at least one live, attenuated dengue virus in a combination wherein three dengue virus serotypes of dengue-1, dengue-2, dengue-3 and dengue-4 are represented in the immunogenic composition and pharmaceutically acceptable excipient,
20. The immunogenic composition according to claim 19, wherein the at least one dengue-dengue chimera comprises a dengue-4 chimera.
21. The immunogenic composition according to claim 20, wherein the dengue-4 chimera has a live, attenuated dengue-2 backbone.
22. The immunogenic composition according to claim 20, wherein the at dengue-4 chimera concentration in the immunogenic composition is at least one log higher than at least one other dengue virus serotype represented in the immunogenic composition.
23. The immunogenic composition according to claim 19, wherein the immunogenic composition is formulated for intradermal (ID), subcutaneous (SC), or intramuscular (IM) administration to a subject.
24. A kit comprising the composition according to claim 19.
25. A vaccine kit comprising; at least a first trivalent immunogenic composition against dengue virus comprising at least three dengue virus serotypes; at least a second immunogenic composition comprising a single dengue-dengue chimera or a single live, attenuated dengue virus; and at least two containers for the immunogenic compositions.
26. The kit according to claim 25, wherein the trivalent dengue virus immunogenic composition comprises a mixture of three different dengue virus comprising dengue-1, dengue-2, dengue-3 and dengue-4.
27. The kit according to claim 26, wherein the trivalent dengue virus immunogenic composition comprises a live, attenuated dengue-2 and a dengue-dengue chimera of dengue-1, dengue-3 or dengue-4.
28. The kit according to claim 25, wherein the trivalent dengue virus immunogenic composition comprises a mixture of three or more different live, attenuated dengue viruses, wherein the mixture comprises at least three dengue virus serotypes comprising dengue-dengue chimeras, wherein the dengue-dengue chimeras comprise dengue virus structural proteins on an attenuated dengue-2 virus backbone, and one or more structural elements of dengue-1, dengue-2, dengue-3 or dengue-4, and one or more structural or non-structural elements of a live, attenuated dengue virus.
29. The kit according to claim 28, wherein the second dengue immunogenic composition comprises a live, attenuated dengue virus immunogenic composition comprising a single live, attenuated dengue virus or a single dengue-dengue chimera.
30. The kit according to claim 25, wherein a dengue-dengue chimera comprises a dengue-4 chimera on a dengue-2 backbone.
31. The kit according to claim 30, wherein the dengue-4 chimera concentration is 2 to 100,000 fold higher concentration than at least one other dengue virus serotype.
32. The kit according to claim 25, wherein the trivalent immunogenic composition comprises dengue-1, dengue-2, and dengue-3; dengue-1, dengue-3, and dengue-4; dengue-1, dengue-2, and dengue-4; or dengue-2, dengue-3 and dengue-4.
33. The kit according to claim 32, wherein the trivalent dengue virus immunogenic compositions comprise unequivalent distribution of the three dengue virus serotypes in the immunogenic composition where concentration of one serotype can vary from 2 to 100,000 fold compared to another.
34. The kit according to claim 25, wherein dengue-2 is present as a live, attenuated dengue-2 in the trivalent immunogenic formulation.
35. The kit according to claim 34, wherein the live, attenuated dengue-2 virus is strain PDK-53.
Description:
PRIORITY
[0001] This application is a U.S. divisional application that claims priority to U.S. patent application Ser. No. 14/652,066, filed Jun. 12, 2015, now U.S. Pat. No. 9,878,031, issued on Jan. 30, 2018, which is a national phase application filed under 35 U.S.C. .sctn. 371 and claims priority to International Application No. PCT/US2013/073757 filed Dec. 07, 2013 and U.S. Provisional Application No. 61/737,679 filed Dec. 14, 2012. These applications are incorporated herein by reference in their entirety for all purposes.
FIELD
[0002] Embodiments of the present invention report compositions and methods for administering a vaccine to a subject against dengue virus serotypes. In some embodiments, vaccine compositions disclosed herein may be administered by subcutaneous, intradermal, intramuscular or other injection or introduction methods against three dengue virus serotypes. In other embodiments, vaccine compositions disclosed herein may be administered to a subject against three dengue virus serotypes (trivalent formulation) followed by a monovalent formulation, bivalent or other trivalent dengue virus vaccine formulation. In certain embodiments, administration of a vaccine to a subject can include administration to two or more anatomical sites of one or more trivalent and optionally, monovalent vaccine compositions. Other embodiments include follow-on injections from within days of a first vaccination to up to 12 months after initial injection(s). In certain embodiments, compositions against dengue virus include trivalent formulations where the formulations comprise chimera constructs having a DEN-2 backbone and for example having combination compositions of chimeras of DEN 1, 3 or 4 on a DEN-2 backbone.
BACKGROUND
[0003] Vaccines for protection against viral infections have been effectively used to reduce the incidence of human disease. One of the most successful technologies for viral vaccines is to immunize animals or humans with a weakened or attenuated strain of the virus (a "live, attenuated virus"). Due to limited replication after immunization, the attenuated strain does not cause disease. However, the limited viral replication is sufficient to express the full repertoire of viral antigens and can generate potent and long-lasting immune responses to the virus. Thus, upon subsequent exposure to a pathogenic strain of the virus, the immunized individual is protected from disease. These live, attenuated viral vaccines are among the most successful vaccines used in public health.
[0004] Dengue viruses are mosquito-borne pathogens of the genus Flavivirus (family Flaviviridae). Four serotypes of dengue virus (often abbreviated "DEN" or "DENV") had been identified, including dengue-1, dengue-2, dengue-3 and dengue-4 (DEN-1 to DEN-4). The flavivirus genome is a single-stranded, positive-sense RNA approximately 11 kb in length, containing a 5'-noncoding region (5'NC); a coding region encoding the viral structural proteins; five nonstructural proteins, designated NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5; and a 3'-noncoding region (3'NC). The viral structural proteins include the capsid, premembrane/membrane and envelope. The structural and nonstructural proteins are translated as a single polyprotein. The polyprotein is then processed by cellular and viral proteases.
[0005] Transmitted by Aedes aegypti mosquitoes to humans in tropical and subtropical regions of the world, dengue viruses cause millions of cases of disease every year, ranging from dengue fever to the often fatal dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Secondary infection of humans with a heterologous serotype of DEN virus may induce an immunopathological response and is considered a possible risk factor for DHF/DSS. Therefore, the need exists for development of a vaccine that confers simultaneous protection against all dengue virus strains.
SUMMARY
[0006] Embodiments of the present invention generally relate to methods and compositions for inducing protection in a subject against multiple a dengue viruses by, for example, by administering a trivalent dengue virus vaccine composition to a subject. In accordance with these embodiments, a trivalent dengue virus vaccine composition includes immunogenic agents to at least three of four dengue virus serotypes or even five of the dengue virus serotypes.
[0007] Some embodiments can include introducing a trivalent dengue virus vaccine composition disclosed herein to a subject in one or more anatomical locations in the subject. In accordance with these embodiments, dengue virus vaccine composition can be introduced to a subject by any method known in the art to, for example, induce neutralizing antibodies against at least three dengue virus serotypes. Other embodiments include administering a trivalent dengue virus vaccine formulation to a subject and then following administration of the trivalent formulation with a monovalent formulation on the same or within 12 months after first administration. Other embodiments include treating a subject with a monovalent dengue virus vaccine composition first and then administering on the same or sometime later, but at least within 12 months of the monovalent dengue virus vaccine formulation at least one trivalent dengue virus vaccine composition.
[0008] Some embodiments concern administering a single trivalent dengue virus vaccine composition to a subject in need thereof to induce a response to three or four dengue virus serotypes.
[0009] In certain embodiments, a vaccine composition can include, but is not limited to, a single dose formulation of a trivalent dengue virus serotype vaccine. In accordance with these embodiments, a trivalent formulation can be a trivalent formulation of dengue-1 (DEN-1); dengue-2 (DEN-2), dengue-3 (DEN-3) and/or dengue-4 (DEN-4). Further, these formulations can be a predetermined ratio of dengue virus serotypes.
[0010] In other embodiments, a vaccine composition may include, but is not limited to; an initial dose of a trivalent dengue virus vaccine composition followed by one or more boosts of the same, or a different trivalent or one or more monovalent dengue-virus vaccine composition administered to a subject in need thereof.
[0011] Other aspects herein can concern inducing a humoral or cellular immune response in a subject by, for example, introducing a vaccine composition to a subject via an intradermal route wherein the vaccine composition includes, but is not limited to, a dengue virus vaccine. In accordance with these embodiments, compositions disclosed can be administered intradermally to a subject for modulating neutralizing antibody production in the subject against three or more dengue virus serotypes. Some aspects concern predetermined composition ratios of three of DEN-1:DEN-2:DEN:3:DEN:4 (e.g. 1:1:1, 1:2:1, 1:1:100,000 etc. or any ratio of three serotypes) of the various serotypes of dengue virus or fragments thereof or attenuated compositions thereof in a single vaccine composition in order to increase cross protection and levels of neutralizing antibodies in a subject against at least three dengue virus serotypes when the subject is administered the single vaccine composition. Other embodiments concern administering a trivalent dengue virus vaccine composition to a subject in need thereof via subcutaneously or by other mode known in the art. In addition, certain embodiments concern treating a subject with at least one additional injection(s) of a trivalent or monovalent dengue virus vaccine composition administered at a separate site from the first injection, for example, in close proximity to the initial injection or in a distant anatomical site on the subject. In addition, at least one additional intradermal injection(s) may be performed less than 30 days after the first administration to the subject while others are performed 30 days and up to 12 months after the first administration of the vaccine.
[0012] In some embodiments, a single dose trivalent vaccine against dengue virus can include constructs of three different dengue virus serotype antigens (e.g. structural proteins) in a single trivalent composition. In accordance with these embodiments, constructs contemplated herein include attenuated dengue-2 virus as a backbone for one or more structural dengue virus proteins capsid (C), premembrane/membrane (prM/M), or envelope (E). In addition, nonstructural proteins may also be included in a construct, including, nonstructural proteins NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5, and 3' NCR. In certain embodiments, a trivalent dengue virus vaccine composition can include constructs having an attenuated dengue-2 virus (e.g. PDK-53) where structural proteins of dengue-2 are replace with one or more structural proteins of DEN-1, DEN-3 or DEN-4. Trivalent dengue virus vaccine compositions can be DENVax 1, 2, 3; DENVax 2, 3, 4; DENVax1, 2, 4 or DENVax1, 3, 4 on an attenuated DEN-2 backbone.
[0013] In certain embodiments, a trivalent dengue virus vaccine composition disclosed herein can include dengue virus constructs in any combination of three where pfus of the various compositions can range from 1 to about 100,000 fold difference depending on desired ratio and endemic conditions in a given location. Some embodiments include up to 100,000 fold pfu difference between DEN-2 and DEN-4 where DEN-4 can be represented up to 100,000 fold higher than DEN-2. Certain embodiments include compositions where dengue virus serotypes are 10 fold higher to 10 fold lower than for example when DENVax1 is 1.25.times.10.sup.4; DENVax2 is 6.04.times.10.sup.4, DENVax3 is 1.30.times.10.sup.5 and DENVax4 is 1.34.times.10..sup.6
[0014] Other embodiments disclosed herein relate to methods and compositions for inducing protection in a subject against all dengue virus serotypes by, for example, administering a trivalent vaccine to a subject against three dengue virus serotypes in two or more doses in one or more than one anatomical location consecutively within a short interval of time. Some embodiments can include introducing a vaccine composition to a subject via intradermal (ID), subcutaneous (SC), or intramuscular (IM) injection in one location and consecutively in another anatomical location by ID, SC, IM or by other introduction method at a second different anatomical location. Other embodiments include using any combination of modes of administration for introducing a dengue virus vaccine of all dengue virus serotypes to a subject where administration of the vaccine occurs at two or more anatomical sites or by two or more different routes consecutively on the same day to the subject.
[0015] In other embodiments, a subject may be administered dengue virus trivalent vaccinations consecutively at two or more anatomical locations, then the subject can be administered at least a third vaccine within 30 days such as about 7, about 14, about 21 or about 28 days later with a composition comprising dengue virus serotypes which can include a monovalent formulation. Subsequent vaccinations may depend on personalized titers of antibodies post dual injection or other criteria such as results of test populations. In certain embodiments, a subsequent vaccination may only include a single dengue serotype (e.g. DEN-4).
[0016] In certain embodiments, the composition introduced to the subject comprises vaccines against three of four dengue virus serotypes, for example a trivalent formulation based on DENVax or another similar formulation. DENVax comprises a tetravalent dengue vaccine of predetermined ratio where the vaccine is made up of constructs on an attenuated DEN-2 backbone (see for example, PCT Application Number PCT/US01/05142 filed on February 16, 2001 incorporated herein by reference in its entirety for all purposes). In other compositions, all dengue vaccine virus serotypes are in equal proportions in the composition. In yet other compositions, each dengue vaccine virus serotype may be in a particular ratio to one another such that introduction of the composition induces sufficient levels of neutralizing antibodies which would provide the subject with sufficient protection against infection (e.g. DEN-1, DEN-2, DEN-3 and/or DEN-4). In accordance with these embodiments, samples from a subject may be analyzed for resistance to dengue infection using standard means known in the art in order to assess immunity to dengue virus serotypes.
[0017] In other embodiments, a vaccine composition can include attenuated dengue virus serotypes in combination with other anti-pathogenic compositions (e.g. Japanese encephalitis, yellow fever, West Nile, influenza, Chikungunya or other).
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The following drawings form part of the present specification and are included to further demonstrate certain embodiments. Some embodiments may be better understood by reference to one or more of these drawings alone or in combination with the detailed description of specific embodiments presented.
[0019] FIG. 1 represents neutralizing antibody titers produced against two different trivalent formulations over time compared to control compositions (e.g. FTA).
DEFINITIONS
[0020] As used herein, "a" or "an" may mean one or more than one of an item.
[0021] As used herein, vessel can include, but is not limited to, test tube, mini- or micro-fuge tube, channel, vial, microtiter plate or container.
[0022] As used herein the specification, "subject" or "subjects" may include but are not limited mammals such as humans or mammals, domesticated or wild, for example dogs, cats, other household pets (e.g., hamster, guinea pig, mouse, rat), ferrets, rabbits, pigs, horses, cattle, prairie dogs, or zoo animals.
[0023] As used herein, "about" or "approximately" can mean plus or minus ten percent.
[0024] As used herein, "Dengue viruses" or "DENs" or "DENVs" are positive, single-stranded RNA viruses belonging to the Flavivirus genus of the flaviviridae family The genomic RNA contains a type I cap at the 5' end but lacks a poly-A tail at the 3' end. The genomic organization consists of the following elements: 5' noncoding region (NCR), structural proteins (capsid (C), premembrane/membrane (prM/M), envelope (E)) and nonstructural proteins (NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5), and 3' NCR. The genomic viral RNA is associated with the capsid proteins so as to form a nucleocapsid. As for the other flaviviruses, the DEN viral genome encodes an uninterrupted coding region which is translated into a single polyprotein.
[0025] As used herein, "attenuated virus" can mean a virus that demonstrates reduced or no clinical signs of disease when administered to a subject such as a mammal (e.g., human or an animal).
[0026] As used herein, "consecutively" can mean in close temporal proximity, usually within a single patient visit and within 24 hours.
[0027] As used herein, "administration" can mean delivery of a vaccine or therapy to an individual animal or human by any one of many methods such as intradermal, subcutaneous, intramuscular, intranasal, inhalation, vaginal, intravenous, oral, buccal, by inhalation, intranasally, or any others known in the art.
DESCRIPTION
[0028] In the following sections, various exemplary compositions and methods are described in order to detail various embodiments. It will be obvious to one skilled in the art that practicing the various embodiments does not require the employment of all or even some of the details outlined herein, but rather that concentrations, times and other details may be modified through routine experimentation. In some cases, well-known methods or components have not been included in the description.
[0029] Certain aspects of the present invention include, but are not limited to, administration of vaccine compositions against dengue virus.
[0030] Embodiments of the present invention generally relate to methods and compositions for inducing protective neutralizing antibodies in a subject against three or more dengue virus serotypes. Other embodiments can include introducing a vaccine composition to a subject via any method known in the art including, but not limited to, intradermal, subcutaneous, intramuscular, intranasal, inhalation, orally, intranasally, vaginal, intravenous, ingested, and any other method wherein the vaccine composition so introduced induces neutralizing antibodies against three or more dengue virus serotypes. In certain embodiments, the vaccine composition comprises a dose of a vaccine against three (trivalent) dengue virus serotypes administered to a subject. In other embodiments, the vaccine composition comprises an initial dose against three dengue serotypes then, one or more of the same other vaccine compositions administered to a subject.
[0031] Vaccines against dengue virus may include a composition comprising predetermined ratios of three of the four live, attenuated dengue vaccine viruses, recombinant dengue vaccine viruses, chimeric viruses or mutants thereof. The ratios of various dengue serotypes may be equivalent or nearly equal in representation or certain serotypes may be represented at higher concentrations than others depending on need or ability to induce a balanced neutralizing antibody response in the subject. In accordance with these embodiments, ratios of different dengue vaccines may differ by 2 to 100,000 fold (e.g. plaque forming units (pfus)) between any two serotypes. This can depend on, for example, number of serotypes represented in the formulation, predetermined response and desired effect. It is contemplated that any dengue vaccine virus serotype formulation may be used to generate a vaccine (e.g. attenuated virus etc.) of use in consecutive administration to a subject in need thereof where the composition includes, but is not limited to, three or more dengue virus serotypes.
[0032] In other embodiments, compositions of dengue virus vaccine formulations may be introduced to a subject prior to, during or after exposure to dengue virus by the subject. In accordance with these embodiments, a subject may receive more than one administration consecutively or more than one administration comprising a dengue virus formulation, optionally, followed by one or more additional administrations at a later time. Intradermal, subcutaneous, intramuscular, intranasal, inhalation, vaginal, intravenous, oral, and any other method of applications of formulations described herein may be combined with any other anti-viral treatment. In some embodiments, it is contemplated that intradermal, subcutaneous, intramuscular introduction of a formulation contemplated herein may be administered to any appropriate region of a subject's body (e.g. arm, shoulder, hip, intranasally etc). In addition, parenteral administration of vaccine formulations may be combined with other modes of administration such as intranasal, pulmonary, oral, buccal, or vaginal in consecutive administrations. In some embodiments, it is contemplated that, after consecutive administrations as described herein primary or booster administrations may occur consecutively on the same day, consecutive days, weekly, monthly, bi-monthly or other appropriate treatment regimen.
[0033] Dengue is endemic in Asia, Central and South America including Colombia, the Caribbean, the Pacific Islands, and parts of Africa and Australia. It is estimated that 3.6 billion people (55% of the world's population) live in areas at risk of dengue virus transmission (DVI). Infection with a dengue virus can result in a range of symptoms, from subclinical disease to debilitating but transient dengue fever to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Currently, there is no therapeutic treatment or prophylactic vaccine for dengue fever. Given the impact of dengue on populations in endemic countries and on travelers to those regions, a vaccine to prevent dengue is needed.
[0034] Dengue is a mosquito borne viral disease, transmitted from human to human primarily by the mosquito, Aedes aegypti. Dengue viruses (DEN) contain a single-stranded, positive-sense RNA genome of approximately 11 kb. The genome consists of three structural proteins, capsid (C), premembrane (prM), and envelope (E), and seven nonstructural proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. There are four different serotypes of dengue viruses, DEN-1, DEN-2, DEN-3 and DEN-4. Primary infection with a given serotype induces lifelong serotype specific immunity. However, there is no long-term cross-protective immunity against the other three dengue virus serotypes, and subsequent infection with an alternate serotype leads to increased probability of more severe disease, such as DHF or DSS.
[0035] Due to the disease enhancement associated with secondary DENV infections, a multivalent (e.g. trivalent) vaccine that stimulates immunity against at least three dengue virus serotypes is contemplated. Several DENV vaccine candidates attenuated by classical serial passage in cell culture have proven unsafe or poorly immunogenic. Chimeric live-attenuated, recombinant DENV vaccines candidates, including viruses based on the attenuated genetic background of yellow fever 17D (YF-17D) vaccine virus, DENV-2 PDK-53 vaccine virus, or DENV-4 containing a 30-nucleotide 3' non-coding region (NCR) deletion are known in the art.
[0036] Live, attenuated dengue viruses of all four serotypes have been developed at Mahidol University in Thailand by passaging the wild-type viruses in cell culture. These are currently the most promising live, attenuated vaccine candidates for immunization against dengue virus infection and/or disease. These vaccine candidates have been designated by a combination of their dengue serotype, the cell line through which they were passaged and the number of times they were passaged.
[0037] Preliminary human clinical trials with these attenuated viruses have indicated that DEN-2 PDK-53 has the lowest infectious dose (50% minimal infectious dose of 5 plaque forming units or PFU) in humans, is strongly immunogenic, and produces no unacceptable clinical symptoms. The DEN-1 PDK-13, DEN-3 PGMK-30/FRhL-3 and DEN-4 PDK-48 vaccine virus candidates have higher 50% minimal infectious doses of 10,000, 3500, and 150 PFU, respectively, in humans.
[0038] The DEN-2 PDK-53 virus vaccine candidate, henceforth abbreviated PDK-53, has several measurable biological markers associated with attenuation, including temperature sensitivity, small plaque size, decreased replication in mosquito C6136 cell culture, decreased replication in intact mosquitoes, loss of neurovirulence for suckling mice and decreased incidence of viremia in monkeys. Clinical trials of the candidate PDK-53 vaccine have demonstrated its safety and immunogenicity in humans. Furthermore, the PDK-53 vaccine induces dengue virus-specific T-cell memory responses in human vaccine recipients. In certain embodiments herein, a chimeric dengue virus construct can include a dengue-2 backbone where PDK-53 has been selected to differ from the known PDK-53 backbone and contain additional mutations that further attenuate the virus.
[0039] Accordingly, there is a need for avirulent, yet immunogenic, dengue viruses to be used in the development of dengue virus vaccines to confer protection against all dengue virus serotypes.
[0040] A challenging issue in the development of an effective live-attenuated dengue virus (DENV) vaccine is the interference between the four dengue vaccine viruses when administered as a tetravalent formulation. Interference is manifest when one or more components of a multivalent mixture will induce lower immune responses than those elicited by each individual monovalent vaccine. Interference has been observed with vaccines for diseases with multiple pathogenic serotypes, such as polio, dengue or others. Due in part to this interference, it was previously discovered that three dose regimen of oral polio vaccine is required to induce adequate immune responses to the three key serotypes. Historically studies with live attenuated tetravalent dengue vaccines have shown that the DENV serotype that elicits the strongest neutralizing antibody response when administered alone tends to dominate immune responses when administered in the context of a multivalent formulation containing other serotypes. As an example, tetravalent mixtures of four different live, attenuated dengue vaccines showed dominant responses to the DEN-3 component and reduced immune responses to DEN-1, -2 and -4 (see for example, Sabchareon, et al., 2002, Kitchener, et al. 2006). As a result of this dominance, clinical development of the tetravalent mixtures was suspended. Interference has been seen with recombinant, live attenuated viruses as well. Interference was documented in tetravalent mixtures of dengue/yellow fever chimeras (Guy, et al. 2009. Evaluation of Interferences between Dengue Vaccine Serotypes in a Monkey Model. Am. J. Trop Med. Hyg. 80: 3012-311). In these studies, two serotypes were found to dominate the responses in tetravalent formulations of ChimeriVax vaccine strains. Interference could be overcome by administering two bivalent vaccine formulations, either in separate anatomical locations or sequentially in time, or by a third administration of the tetravalent formulation after one year. Similarly, it was demonstrated that improved multivalent responses with tetravalent recombinant vaccine strains (in this case, formulations containing DENV or chimeric DENV with deletions in the 3' non-coding region) could be obtained only with a prolonged four month internal between the first and second administration. (Blaney, et al., 2005. Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys. J. Virology 79: 5516-5528).
[0041] Certain embodiments disclosed herein concern derivatives of DENVax (a tetravalent vaccine composition). DENVax is a dengue vaccine that consists of a mixture of four recombinant dengue virus strains designed to generate immune responses to the four dengue serotypes (DEN-1, DEN-2, DEN-3 and DEN-4). Not to be bound by any limitations to a particular tetravalent formulation, DENVax.TM., the dengue serotype 2 vaccine component (DENVax-2) corresponds to an attenuated DEN-2 PDK-53 strain. This construct has already been investigated in many clinical studies. The other dengue vaccine strains (DENVax-1, DENVax-3 and DENVax-4) are chimeras consisting of the DEN-1, DEN-3 or DEN-4 structural pre-membrane (prM) and envelope (E) protein genes cloned into a DEN-2 PDK-53 non-structural gene backbone. These recombinant viruses express the surface antigens of DEN-1, DEN-3 or DEN-4 and retain the genetic alterations responsible for the attenuation of the DEN-2 PDK-53 strain. In certain embodiments, DENVax can be used as an example of a trivalent live, attenuated dengue vaccine having three of four dengue virus serotypes represented in one vaccine composition at various ratios. Other embodiments relate to optimizing tetravalent vaccine administrations. Yet other embodiments relate to DENVax.TM. immunization methods.
[0042] In some embodiments, a mixture of three or more attenuated dengue viruses comprises one or more attenuated dengue-2 viruses and one or more dengue-dengue chimeric viruses further comprising capsid and non-structural proteins of the attenuated dengue-2 virus and pre-membrane and envelope proteins of at least a second dengue virus.
[0043] In certain embodiments, a chimeric construct of the instant application can include the pre-membrane (PM) and envelope (E) proteins of at least a second dengue virus are dengue-2, dengue-3 or dengue-4 when the attenuated dengue virus is dengue-1; or dengue-1, dengue-3 or dengue-4 when the attenuated dengue virus is dengue-2; or dengue-1, dengue-2 or dengue-4 when the attenuated dengue virus is dengue-3; or dengue-1, dengue-2 or dengue-3 when the attenuated dengue virus is dengue-4.
[0044] In other embodiments, the composition introduced to the subject comprises vaccines against three of dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). In other embodiments, a composition contemplated herein can include a modified formula of DENVax where three of four dengue virus serotypes are represented or other similar formulation. In some compositions, vaccine viruses against all dengue serotypes are in equal proportions in the composition. In yet other compositions, each dengue vaccine virus serotype may be in a particular ratio to one another such that introduction of the composition provides the subject with sufficient levels of neutralizing antibodies against all dengue viruses (e.g. DEN-1, DEN-2, DEN-3, DEN-4).
[0045] Certain embodiments disclosed herein relate to methods and compositions for a rapid induction of protection in a subject against all dengue virus serotypes by, for example, administering a vaccine to a subject against three of four dengue virus serotypes in more than one anatomical location consecutively on the same day. Some embodiments can include introducing a vaccine composition to a subject via intradermal (ID) or subcutaneous (SC) injection or other administration mode in one anatomical location then introducing at least a second vaccine composition at another anatomical location by ID, SC or other administration mode. Some embodiments include using any combination of modes of administration for introducing a dengue virus vaccine of all dengue virus serotypes using a trivalent formulation to a subject where administration of the vaccine occurs at two or more anatomical sites or by two or more different routes on day 0 to the subject. Some embodiments include using the same mode of administration but at different anatomical locations.
[0046] Some dengue virus vaccine compositions described herein range in dosage from from 10.sup.2 to 5.times.10.sup.6 PFU for each serotype in a single trivalent composition. Other compositions (e.g. follow-on vaccinations) contemplated herein include compositions that have dosages less than or more than this range based on immune response in the subject after primary immunization. In certain embodiments, ratios can vary for the various Dengue vaccine virus serotypes depending on need and immune response in a subject.
[0047] In certain embodiments, compositions introduced on the first vaccination or in any follow-on vaccination contemplated herein may include one trivalent dengue virus composition. In accordance with these embodiments, the composition can include three of four dengue virus serotypes of a DENVax composition or other similar trivalent formulation of equal or equivalent ratios or at predetermined serotype ratios. Other embodiments, can include using different formulations (e.g. serotype ratios) for each of the vaccine compositions administered at the primary vaccination or any follow-on vaccinations (e.g. less than 30 days later).
[0048] Some embodiments herein include treating a subject in need of such a vaccine, on day 0 at two or more anatomical locations then administering at least a second vaccine within 30 days such as about 7, about 14, about 21 or about 28 days later with a composition comprising dengue virus serotypes which may or may not have all serotypes. In certain embodiments, each vaccination has all dengue virus serotypes represented in the vaccine formulation. Vaccine compositions of follow-on administration disclosed herein may include two or more dengue virus serotypes at a predetermined ratio for the subsequent administration(s). In certain vaccine compositions, the ratio of three of four of DEN-1:DEN-2:DEN-3:DEN-4 or even DEN-5 can be 3:3:3, 4:3:4, 5:4:5,:4:5:5, 5:5:5, 1:10:100 or other ratio where the ratio between 2 serotypes can be about 2 to about 100,000 fold difference in a single composition. In certain embodiments a dengue serotype ratio can be DEN-1 at 2.times.10.sup.4: DEN-2 at 5.times.10.sup.4: DEN-3 at 1.times.10.sup.5: DEN-4 at 3.times.10.sup.5 PFUs; DEN-1 at 8.times.10.sup.3: DEN-2 at 5.times.10.sup.3: DEN-3 at 1.times.10.sup.4: DEN-4 at 2.times.10.sup.5 PFUs and in any combination of three of the four dengue virus serotypes. In certain embodiments, a trivalent formulation can contain a ratio that includes a higher ratio for dengue-4 than for other serotypes. In some compositions, all dengue vaccine virus serotypes are in equal proportions in the composition. In yet other compositions, each dengue vaccine virus serotype may be in a particular ratio to another serotype such that introduction of the composition provides the subject with adequate or more than adequate levels of neutralizing antibodies which confer protection against all dengue viruses (e.g. any combination of three of the four of Dengue 1, 2, 3 and 4). For example, if after receiving two or more consecutive vaccinations on day 0 at two or more anatomical locations, the subject has lower protection to one or more particular dengue virus serotypes, then a booster for that subject can contain an increased concentration of the one or more dengue vaccine virus serotype (that demonstrated lower neutralizing antibodies) to provide better protection against all dengue virus types. In accordance with these embodiments, samples from a subject may be analyzed for an immune response to dengue serotype infection (e.g. DEN-1, -2, -3, -4) using standard means known in the art.
[0049] In certain embodiments, the vaccine composition can be simultaneously or consecutively introduced to a subject intradermally in multiple anatomical locations to, for example, protect against all dengue serotypes (e.g. cross protection). In certain embodiments, a vaccine composition can include, but is not limited to, a single formulation of three of four dengue vaccine virus serotypes administered to a subject capable of providing full protection against infection by all dengue virus serotypes. In other embodiments, a vaccine composition can include attenuated dengue virus serotypes in combination with other anti-pathogenic compositions (e.g. Japanese encephalitis, West Nile, influenza etc.). Compositions contemplated herein can be administered by any method known in the art including, but not limited to, intradermal, subcutaneous, intramuscular, intranasal, inhalation, vaginal, intravenous, ingested, and any other method. Introduction in two or more anatomical sites can include any combination administration including by the same mode in two or more anatomical sites or by two different modes that include two separate anatomical sites. In accordance with these embodiments, two or more anatomical sites can include different limbs.
[0050] For example, if a subject, after receiving two or more consecutive vaccinations on day 0 at two or more anatomical locations and the subject does not induce poor levels of neutralizing antibodies to one or more particular dengue virus serotypes, then a booster vaccination for that subject can contain an increased concentration of the one or more dengue vaccine virus serotype (that demonstrated lower levels of neutralizing antibodies) to provide complete protection against infection by all dengue virus types. In accordance with these embodiments, samples from a subject may be analyzed for resistance to dengue infection using standard means known in the art.
[0051] In certain embodiments, vaccine compositions disclosed herein can be chimeric constructs that can include a mixture of constructs that make up three dengue serotypes in a vaccine composition for administration to a subject. In other embodiments, dengue virus vaccines can include constructs having an attenuated flavivirus backbone with various dengue serotype substitutions representing each of the four serotypes where the constructs can be mixed in a composition for administration as a vaccine.
[0052] Trivalent formulations, e.g. using a variation of DENVax, can be prepared by mixing predetermined amounts of each monovalent vaccine component. Based on input titer of each vaccine component, a defined volume of monovalent vaccines can be added to a final volume of either 0.1mL (e.g. for intradermal) or 0.5mL (e.g. for subcutaneous) vaccine formulation. The remaining volume of the tetravalent DENVax.TM. vaccine can be composed of diluent containing Trehalose (15%) F127 (1%) and human serum albumin (0.1%) in a saline buffer to stabilize the live, attenuated vaccine formulation. FTA (F127: Trehalose: Albumin)
Methods
Construction of Flavivirus Chimeras
[0053] The flavivirus chimeras described herein can be produced by splicing one or more of the structural protein genes of the flavivirus against which immunity is desired into a PDK-53 dengue virus genome backbone, or the equivalent thereof as described above, using recombinant engineering techniques well known to those skilled in the art to remove the corresponding PDK-53 gene and replace it with the desired gene.
[0054] Alternatively, using the sequences, nucleic acid molecules encoding the flavivirus proteins may be synthesized using known nucleic acid synthesis techniques and inserted into an appropriate vector. Avirulent, immunogenic virus is therefore produced using recombinant engineering techniques known to those skilled in the art.
[0055] As recited above, a target gene to be inserted into the backbone encodes a flavivirus structural protein. In accordance with these embodiments, a flavivirus gene to be inserted is a gene encoding a C protein, a PrM protein and/or an E protein. The sequence inserted into the dengue-2 backbone can encode both the PrM and E structural proteins. The sequence inserted into the dengue-2 backbone can encode the C, prM and E structural proteins. The dengue virus backbone is the PDK-53 dengue-2 virus genome and includes either the spliced genes that encode the C, PrM and/or E structural proteins of dengue-1 (DEN-2/1), the spliced genes that encode the PrM and/or E structural proteins of dengue-3 (DEN-2/3), or the spliced genes encode the PrM and/or E structural proteins of dengue-4 (DEN-2/4). In a particular embodiment of this invention, the spliced gene that encodes the structural protein of dengue-3 virus directs the synthesis of an E protein that contains a leucine at amino acid position 345.
[0056] In a particular embodiment, the chimera of this invention encodes the C structural protein of dengue-2 virus and directs the synthesis of a C protein that contains a serine at amino acid position 100 and comprises a spliced gene encoding the structural proteins of dengue-4 which directs the synthesis of an E protein that contains a leucine at amino acid position 447.
[0057] In a further embodiment, the chimera of this invention encodes the C structural protein of dengue-2 virus and directs the synthesis of a C protein that contains a serine at amino acid position 100 and comprises a spliced gene encoding the structural proteins of dengue-4 which directs the synthesis of an E protein that contains a leucine at amino acid position 447 and a valine at amino acid position 364. The structural proteins described herein can be present as the only flavivirus structural protein or in any combination of flavivirus structural proteins in a viral chimera of this invention.
[0058] Certain chimeras contemplated herein are engineered by recombination of full genome-length cDNA clones derived from both DEN-2 16681 wild type virus and either of the PDK-53 dengue-2 virus variants (-E or -V). The uncloned PDK-53 vaccine contains a mixture of two genotypic variants, designated herein as PDK-53-E and PDK-53-V. The PDK-53-V variant contains all nine PDK-53 vaccine-specific nucleotide mutations, including the Glu-to-Val mutation at amino acid position NS3-250. The PDK-53-E variant contains eight of the nine mutations of the PDK-53 vaccine and the NS3-250-Glu of the parental 16681 virus. Infectious cDNA clones are constructed for both variants, and viruses derived from both clones are attenuated in mice. The phenotypic markers of attenuation of DEN-2 PDK-53 virus include small plaque size, temperature sensitivity (particularly in LLC-MK.sub.2 cells), limited replication (particularly in C6/36 cells), attenuation for newborn mice (specifically loss of neurovirulence for suckling mice) and decreased incidence of viremia in monkeys. The chimeras that are useful as vaccine candidates are constructed in the genetic backgrounds of the two DEN-2 PDK-53 variants which all contain mutations in nonstructural regions of the genome, including 5'NC-57 C-to-T (16681-to-PDK-53) in the 5' noncoding region, as well as mutations in the amino acid sequence of the nonstructural proteins, such as, for example, NS1-53 Gly-to-Asp and NS3-250 Glu-to-Val.
[0059] In certain embodiments, an immunogenic composition that includes chimeric dengue constructs of the present invention can be a combination of three or more of DEN-1, DEN-2, DEN-3 or DEN-4 to confer simultaneous protection against all four dengue virus serotypes in a single vaccine administration. In other embodiments, an immunogenic composition including combinations of three DEN-1, DEN-2, DEN-3 and DENV-4 constructs of embodiments disclosed herein can be administered to a subject to induce improved immunogenic responses against each dengue virus serotype and where immune response interference to the dengue virus constructs is reduced.
[0060] In certain embodiments, dengue virus constructs can include a dengue-dengue chimeric construct having adaptive mutations in the structural or non-structural regions of the various dengue virus serotypes. In other embodiments, a chimeric construct can include a DEN-2 backbone where structural or non-structural regions of DENV-1, -3, -4 are substituted for DEN-2 structural or non-structural regions. In accordance with these embodiments, a DEN-2 backbone can include any live attenuated DEN-2 virus. In other embodiments, a DEN-2 backbone can include live attenuated DEN-2 PDK-53 virus as a backbone where the live attenuated DEN-2 PDK virus further includes structural proteins of one or more of prM (premembrane) and E (envelope) structural proteins of DEN-1, DEN-3 or DEN-4. In addition, a DEN-2 PDK-53 backbone can include additional mutations or reversions of mutations of DEN-2 PDK-53 generating a novel construct in order to enhance in vitro growth, or in vivo the immune response to DEN-1, DEN-3 or DEN-4 in a subject upon administration.
[0061] In some embodiments, a current dengue chimeric construct denoted as DENVax-4 strain was modified to contain a capsid/PrM junction of the DEN-2 backbone to be more genetically similar to that of DENV-4 instead of DEN-2 in order to improve replication efficiency of the virus both in vitro for production and in vivo as a construct of use for inducing an immune response to DENV-4. The current strain of DEN-4, DENVax-4, has a capsid/PrM sequence that is identical to DEN-2 instead of DEN-4, possibly creating an inefficient transcription and translation from the genomic RNA, which is different than that of wild type DENV-4. It is contemplated that these DENV-4 constructs can be used in any trivalent composition contemplated herein, in combination with DEN-1, DEN-2 and DEN-3 as live, attenuated and/or chimeric dengue-dengue constructs.
[0062] In some embodiments, structural protein genes can include prM and E genes of DENV-4 on another dengue virus backbone (e.g. dengue-2, DEN-2 PDK-53), making a dengue-dengue chimera. For example, a DEN-4 construct, in certain embodiments can include those construct termed DENVax-4e (Capsid 107 Cysteine to Tyrosine; DenVax-4b backbone, modifications at Capsid/prM junction), DENVax-4f (where the PDK-53 backbone NS2A and NS4A mutations are reverted to that of 16681) or DENVax-4h (Envelope 417 Glu to Lys) where for certain constructs the DEN-2 PDK-53 backbone has one or more reversions to wild-type DEN-2 (e.g. in the non-coding region (NCR) or a non-structural region (NS2 etc.)) and one or more mutations in the DENV-4 structural region (e.g. prM or E), while encoding one or more structural proteins of DENV-4 (e.g. strain 1036). A modified DENV-4 construct disclosed herein can include a modified attenuated DEN-2 PDK-53 backbone, having one or more modified structural proteins of DENV-4 strain 1036. In some embodiments, one or more mutations present in live, attenuated DEN-2 PDK-53 virus can be reverted back to a wildtype nucleic acid (which may be a silent mutation) or another nucleic acid to produce constructs herein that generate a modified DEN-2/DENV-4 construct having increased replication ability and immunogenicity without affecting its attenuation or safety but may affect growth and/or replication of the DEN-4 virus. In certain embodiment, the reversions may lead to increased growth and/or replication.
[0063] In other embodiments, trivalent compositions disclosed herein can include a modified DENV-4 (or DENV-1 or DENV-3) construct can incorporate mutations introduced to one or more structural regions and/or non-structural regions of the dengue serotype in order to generate constructs inducing an improved immunological response while maintaining safety and viral attenuation. For example, a modified or mutated dengue-dengue chimera of DEN-2/DENV-4 may contain mutations at one or more non-structural regions of a DEN-2 PDK-53 backbone, such as NS2A, and NS4A, and/or mutations at 5' non-coding region (5'NCR). In another embodiment, a modified DENV-4 chimera construct can include NS2A and NS4A of DEN-2 16681 by reverting mutations at NS2A and NS4A of PDK-53 (e.g. an M-L substitution at NS4A). Some embodiments include a modified DENV-4 chimera construct having 5'NCR, NS2A and NS4A of DEN-2 16681 by reverting corresponding mutations in the DEN-2 PDK-53 backbone of a target construct. Other embodiments can include a modified DENV-4 chimera construct having 5'NCR of DEN-2 16681 by reverting corresponding mutations in the DEN-2 PDK-53 backbone. A modified DEN-4 chimera construct can also include DEN-2 PDK-53 backbone, and encode one or more structural proteins of DEN-4 strain H241. It is contemplated that, to induce an immune response, any DEN-4 structural protein can be substituted for structural regions of a chimeric virus containing a dengue -2 serotype backbone (e.g. PDK-53 or modified PDK-53). In some embodiments, a modified DEN-4 construct contains live attenuated DEN-2 PDK-53 as a backbone, and DEN-4, DEN-2 or DEN-3 structural proteins where mutations can be introduced to modify structural regions of a DEN-4 (e.g. strain 1036) or DEN-1 or DEN-3 strain.
[0064] In other embodiments, trivalent compositions can include constructs with mutations introduced to capsid/prM junction amino acid sequences of a DENV virus in order to increase immunogenicity of a construct containing such a mutation. For example, a mutation in DEN-4 can be a Cys-Tyr mutation at capsid position 107 of the DEN-4. In other embodiments, it is contemplated that the cysteine in position 107 can be mutated to any other aromatic amino acid with a hydrophobic side chain (see for example DEN-4e). Other DEN-2 PDK-53 reversion of a chimeric construct can be found in NS2A or NS4A. Yet other embodiments include a DEN-4 construct where a DEN-2 backbone comprises PDK-53 (MVS, SEQ ID NO:21) where amino acid positions 102-107 of the capsid region of PDK-53 are converted to a homologous DEN-4 counterpart amino acid to generate DENV-4b. These backbone constructs can then further comprise a cysteine in the capsid region to aromatic amino acid in position (e.g. tyrosine, tryptophan etc). In certain embodiments, this construct is represented by SEQ ID NO:22 or SEQ ID NO:23.
[0065] Other DENV-4 constructs of use in trivalent compositions disclosed herein can include a virus construct with an amino acid substitution at Envelope position 417. For example, DEN-4 strain 1036 strain sequence or equivalent strain position thereof where a PDK-53 (MVS DEN2/4, SEQ ID NO:21) backbone of Dengue-2 with DEN-4 structural proteins is provided. Embodiments include further mutating Envelope position 417 from a negative to a positively charged side-chain amino acid (e.g. lysine). It is contemplated that any charged side chain will provide increased immunogenicity of the DEN-4 construct without affecting its safety or attenuation. In certain embodiments, this construct is represented by SEQ ID NO:24 or SEQ ID NO:25.
[0066] In certain embodiments, DEN-2 PDK-53 reversions of a chimeric DENV construct have the 5' NC, NS1 and NS3 mutations found in DEN-2 PDK-53 MVS while having other reversions or mutations that differ from DEN-2 PDK-53. It has been demonstrated that these three mutations can be important for attenuation (e.g. small plaque size, reduced growth rate, lower titer, increased temperature sensitivity and decreased neurovirulence compared to a control).
[0067] In other embodiments, DEN-2 PDK-53 genome backbones can be used to generate chimeric constructs of DEN-1 and DEN-3, where one or more structural protein genes of DEN-2 PDK-53 genome can be replaced by one or more structural protein genes of DEN-1 and DEN-3. These constructs can include a combination of both DEN-1 and DEN-3 in a single chimera having a DEN-2 PDK-53 backbone. In some embodiments, a structural protein can be the C, prM or E protein of DEN-1 and/or DEN-3. In certain embodiments, structural protein genes include the prM and E genes of DEN-1 or DEN-3. These hybrid/chimeric viruses express the surface antigens of DEN-1, DEN-3 or DENV-4 while retaining the attenuation phenotypes of the parent DEN-2. In certain embodiments, these constructs can be represented by SEQ ID NO:15, DEN-2/DEN-1 and SEQ ID NO: 19, DEN-2/DEN-3 where these constructs can be used in di-, tri or tetravalent compositions disclosed herein.
[0068] In some embodiment, constructs disclosed herein can include chimeric constructs of DENV-4, DEN-2, DEN-1, and DEN-3 expressing surface antigens of DEN-1, DEN-3 and DENV-4 using attenuated DEN-2 PDK-53 virus as a backbone.
[0069] Suitable chimeric viruses or nucleic acid chimeras containing nucleotide sequences encoding structural proteins of other flaviviruses or dengue virus serotypes can be evaluated for usefulness as vaccines by screening them for the phenotypic markers of attenuation that indicate avirulence and by screening them for immunogenicity. Antigenicity and immunogenicity can be evaluated using in vitro or in vivo reactivity with flavivirus antibodies or immunoreactive serum using routine screening procedures known to those skilled in the art.
Flavivirus Vaccines
[0070] Chimeric viruses and nucleic acid chimeras provide live, attenuated viruses useful as immunogens or vaccines. In a preferred embodiment, chimeras exhibit high immunogenicity while at the same time producing no dangerous pathogenic or lethal effects. Chimeric viruses or nucleic acid chimeras of this invention can comprise the structural genes of either wild-type or attenuated virus in a virulent or an attenuated DEN-2 virus backbone. For example, the chimera may express the structural protein genes of wild-type DEN-1 16007 virus or its candidate PDK-13 vaccine derivative in either of the DEN-2 PDK-53 backgrounds.
[0071] All of the chimeric DEN-2/1 viruses containing the C, prM and B proteins of either DEN-1 16007 virus (DEN-2/1-EP and -VP chimeras) or PDK-13 virus (DEN-2/1-EV and -VV) chimeras) in the backbones of DEN-2 PDK-53 retain all of the phenotypic attenuation markers of the DEN-2 PDK-53 virus. The chimeric DEN-2/1-EP and -VP viruses, which contain the C, prM and E proteins of DEN-1 16007 virus are more genetically stable after passing in cell culture than the DEN-2/1-EV and -VV viruses. The immunogenicity of the chimeric viruses expressing the structural proteins of DEN-1 16007 virus was higher as compared with the neutralizing antibody titers elicited by the PDK-13 vaccine virus and the chimeras expressing the structural proteins of the PDK-13 virus. Thus, the chimeric DEN-2/1-EP and -VP viruses, which express the structural genes of wild-type DEN-1 16007 virus within the genetic background of the two DEN-2 PDK-53 variants, are potential DEN-1 vaccine candidates that are superior to the candidate PDK-13 vaccine. These two chimeras replicate well in LLC-MK.sub.2 cells and retain the attenuation markers associated with DEN-2 PDK-53 virus, including small plaque size, temperature sensitivity, restricted replication in mosquito cells and attenuation for mice. They are at least as immunogenic as wild-type DEN-1 16007 virus in mice.
[0072] Other examples, such as DEN-2/3 and DEN-2/4 chimeras, are chimeric viruses containing structural protein genes from wild-type DEN-3 or DEN-4 virus within the DEN-2 PDK-53 backbones, are suitable vaccine candidates which retain all of the attenuated phenotypic markers of the DEN-2 PDK-53 viruses, while providing immunogenicity against DEN-3 or DEN-4 virus. The strategy described herein of using a genetic background that contains the determinants of attenuation in nonstructural regions of the genome to express the structural protein genes of heterologous viruses has lead to development of live, attenuated flavivirus vaccine candidates that express wild-type structural protein genes of optimal immunogenicity. Thus, vaccine candidates for immunogenic variants of multiple flaviviral pathogens can be designed.
[0073] Viruses used in the chimeras described herein are typically grown using techniques known in the art. Virus plaque titrations are then performed and plaques counted in order to assess the viability and phenotypic characteristics of the growing cultures. Wild type viruses are passaged through cultured cell lines to derive attenuated candidate starting materials.
[0074] Chimeric infectious clones are constructed from the various dengue serotype clones available. The cloning of virus-specific cDNA fragments can also be accomplished, if desired. The cDNA fragments containing the structural protein or nonstructural protein genes are amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) from dengue virus RNA with various primers. Amplified fragments are cloned into the cleavage sites of other intermediate clones. Intermediate, chimeric dengue virus clones are then sequenced to verify the accuracy of the inserted dengue virus-specific cDNA.
[0075] Full genome-length chimeric plasmids constructed by inserting the structural protein or nonstructural protein gene region of dengue serotype viruses into vectors are obtainable sing recombinant techniques well known to those skilled in the art.
Nucleotide and Amino Acid Analysis
[0076] A comparison of the critical nucleotide and amino acid substitutions that have been discovered between the parent strain and the attenuated virus are incorporated herein by reference. The sequence of the DEN-2 cDNA amplicons was amplified from DEN-2 viral genomic RNA by reverse transcriptase-polymerase chain reaction (RT-PCR).
[0077] Unlike PDK-53, which contains no amino acid mutations in the E protein relative to wild type dengue-2 virus, DEN-1, DEN-3 and DEN-4 attenuated viruses all have amino acid mutations in the E protein. The wild-type DEN-3 16562 was shown to include traces of a variant comprising a T at nucleotide position 1521 which directs incorporation of a leucine at polyprotein position 476, amino acid residue position 476 of the E protein.
[0078] Each of the latter three viruses possesses a Glu-to-Lys (parent-to-vaccine) mutation in the E protein, although the mutation is located at a different amino acid residue in the E protein. This substitution causes a shift from a negatively charged amino acid to a positively charged one. The Glu-to-Lys substitution in the E protein of DEN-4 vaccine virus was the only mutation present in the E protein, while the E proteins of DEN-1 and DEN-3 vaccine viruses had five and three amino acid mutations, respectively.
[0079] The NS1-53 mutation in the DEN-2 PDK-53 vaccine virus is significant for the attenuated phenotype of this virus, because the NS1-53-Gly of the DEN-2 16681 virus is conserved in nearly all flaviviruses, including the tick-borne viruses, sequenced to date. The mutations that occurred in the NS2A, NS2B, NS4A, and NS4B proteins of the DEN-1, -2, -3 and -4 attenuated strains were all conservative in nature. The NS4A-75 and NS4A-95 mutations of DEN-2 and DEN-4 vaccine viruses, respectively, occurred at sites of amino acid conservation among dengue viruses, but not among flaviviruses in general.
[0080] The flaviviral NS3 protein possesses at least two recognized functions: the viral proteinase and RNA helicase/NTPase. The 698-aa long (DEN-2 virus) NS3 protein contains an amino-terminal serine protease domain (NS3-51-His, -75-Asp, -135-Ser catalytic triad) that is followed by sequence motifs for RNA helicase/NTPase functions NS3-196-GAGKT, -284-DEAH, -459-GRIGR. None of the mutations in the NS3 proteins of DEN-1, DEN-2, or DEN-3 virus occurred within a recognized motif. The NS3-510 Tyr-to-Phe mutation in DEN-1 PDK-13 virus was conservative. Since the wild-type DEN-2, -3 and -4 viruses contain Phe at this position, it is unlikely that the Tyr-to-Phe mutation plays a role in the attenuation of DEN-1 virus. The NS3-182 Glu-to-Lys mutation in DEN-1 PDK-13 virus occurred at a position that is conserved as Asp or Glu in most mosquito-borne flaviviruses and it may play some role in attenuation. This mutation was located 15 amino acid residues upstream of the GAGKT (helicase motif. As noted in previous reports, the NS3-250-Glu in DEN-2 16681 virus is conserved in all mosquito-borne flaviviruses except for yellow fever virus.
Nucleic Acid Amplification
[0081] Nucleic acids may be used in any formulation or used to generate any formulation contemplated herein. Nucleic acid sequences used as a template for amplification can be isolated viruses (e.g. dengue viruses), according to standard methodologies. A nucleic acid sequence may be genomic DNA or fractionated or whole cell RNA. Where RNA is used, it may be desired to convert the RNA to a complementary cDNA. In some embodiments, the RNA is whole cell RNA and is used directly as the template for amplification. Any method known in the art for amplifying nucleic acid molecules is contemplated (e.g., PCR, LCR, Qbeta Replicase, etc).
Expressed Proteins or Peptides
[0082] Genes can be expressed in any number of different recombinant DNA expression systems to generate large amounts of the polypeptide product, which can then be purified and used in methods and compositions reported herein. Any method known in the art for generating and using constructs is contemplated. In certain embodiments, genes or gene fragments encoding one or more polypeptide may be inserted into an expression vector by standard cloning or subcloning techniques known in the art.
[0083] Proteins, peptides and/or antibodies or fragments thereof may be detected or analyzed by any means known in the art. In certain embodiments, methods for separating and analyzing molecules may be used such as gel electrophoresis or column chromatography methods.
Electrophoresis
[0084] Electrophoresis may be used to separate molecules (e.g., large molecules such as proteins or nucleic acids) based on their size and electrical charge. There are many variations of electrophoresis known in the art. A solution through which the molecules move may be free, usually in capillary tubes or it may be embedded in a matrix or other material known in the art. Common matrices can include, but are not limited to, polyacrylamide gels, agarose gels, mass spec, blotting and filter paper.
[0085] Some embodiments, using a gene or gene fragment encoding a polypeptide may be inserted into an expression vector by standard subcloning techniques. An expression vector may be used which produces the recombinant polypeptide as a fusion protein, allowing rapid affinity purification of a peptide or protein. Examples of such fusion protein expression systems are the glutathione S-transferase system (Pharmacia, Piscataway, N.J.), the maltose binding protein system (NEB, Beverley, Mass.), the FLAG system (IBI, New Haven, Conn.), and the 6.times.His system (Qiagen, Chatsworth, Calif.).
Pharmaceutical Formulations
[0086] Any pharmaceutical formulation known in the art for a vaccine is contemplated herein. In certain embodiments, a formulation disclosed herein contains chimeric or live, attenuated virus that represent three dengue virus serotypes in various ratios in a single vaccine or one to all serotypes for follow-on compositions. It is contemplated that formulations can contain other agents of use in vaccination of a subject including, but not limited to other active or inactive ingredients or compositions known to one skilled in the art.
[0087] All contemplated vaccinal viruses herein can be administered in the form of vaccinal compositions which can be prepared by any method known to one skilled in the art. In certain embodiments, the virus compositions are lyophilized and are mixed with a pharmaceutically acceptable excipient (e.g. water, phosphate buffered saline (PBS), wetting agents etc.) In other embodiments, vaccine compositions can include stabilizers that are known to reduce degradation of the formulation and prolong shelf-life of the compositions.
[0088] In other embodiments, an adjuvant may be added to the composition to induce, increase, stimulate or strengthen a cellular or humoral immune response to administration of a vaccination described herein. Any adjuvant known in the art that is compatible with compositions disclosed herein is contemplated.
[0089] Some embodiments herein concern amounts or doses or volumes of administration of a trivalent dengue virus composition and the amount or dose can depend on route of administration and other specifications such as the subject getting the vaccine (e.g. age, health condition, weight etc.).
[0090] It is contemplated herein that compositions described can be administered to a subject living in an area having dengue virus, a subject traveling to an area having dengue virus or other subject such as any human or animal capable of getting dengue fever or other dengue virus condition. In certain embodiments, it may be recommended that a subject traveling to an area having dengue virus is administered one or more vaccine compositions (e.g. or two or more on Day 0) about 1 to about 3 months prior to dengue virus exposure. Vaccines herein can be administered as a prophylactic treatment to prevent infection in adults and children. A subject can be naive or non-naive subject with respect to exposure to dengue virus and vaccine regimens disclosed herein.
Kits
[0091] Other embodiments concern kits of use with the methods (e.g. methods of application or administration of a vaccine) and compositions described herein. Some embodiments concern kits having vaccine trivalent compositions of use to prevent or reduce the incidence of a subject having been exposed or suspected of being exposed to one or more dengue viruses to get an infection from the virus. In certain embodiments, a kit may contain one or more than one formulation of dengue virus serotype(s) (e.g. live, attenuated viruses or chimeric constructs to make a trivalent formulation, DENVax) at predetermined ratios of the dengue virus serotypes. Kits can be portable, for example, able to be transported and used in remote areas such as military installations or remote villages in dengue endemic areas. Other kits may be of use in a health facility to treat a subject having been exposed to one or more dengue viruses or suspected of being at risk of exposure to dengue virus.
[0092] Kits can also include a suitable container, for example, a vessel, vials, tubes, mini- or microfuge tubes, test tube, flask, bottle, syringe or other container. Where an additional component or agent is provided, the kit can contain one or more additional containers into which this agent or component may be placed. Kits herein will also typically include a means for containing the agent (e.g. a vessel), composition and any other reagent containers in close confinement for commercial sale. Such containers may include injection or blow-molded plastic containers into which the desired vials are retained. Optionally, one or more additional agents such as immunogenic agents or other anti-viral agents, anti-fungal or anti-bacterial agents may be needed for compositions described, for example, for compositions of use as a vaccine against one or more additional microorganisms.
[0093] In other embodiments, kits can include devices for administering one or more vaccination to a subject such as an ID, SQ, IM, an inhaler, intranasal applicator or other device for administering a vaccine composition disclosed herein.
[0094] The following examples are included to demonstrate certain embodiments presented herein. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered to function well in the practices disclosed herein. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the certain embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope herein.
EXAMPLES
Example 1
[0095] In one exemplary method, dengue virus trivalent vaccine compositions studies were performed using various trivalent dengue virus formulations alone, in multiple doses or in combination with follow-on monovalent dengue virus formulations. In certain exemplary methods, the following concentrations of dengue virus serotypes were used: DENVax-1: 1.times.10.sup.5PFU, DENVax-2; 1.times.10.sup.5PFU, DENVax3: 1.times.10.sup.5PFU, and DENVax4: 1.times.10.sup.5PFU. See for example Table 1 and 2. In certain embodiments various dengue-4 serotypes can be combined with live, attenuated dengue-2 and a chimeric construct of dengue-1 in order to induce immunity in the subject against all four serotypes.
[0096] Animals: Cynomolgus macaques
[0097] Route of Immunization & Challenge: Subcutaneous (0.5mL)
[0098] Vaccination Schedule & Dose: Days 0, 91 (DENVax-HD+)
[0099] Challenge: Day 120
[0100] Dose: DENV-2 (105pfu), DENV-4 (106pfu)
[0101] Sampling
[0102] Viremia: qRT-PCR using primer for E-gene
[0103] Pre & Post primary vaccination: 0, 5, 8, 11, 14, 17, 20, 23, 25
[0104] Pre & Post Boost: 91, 94, 98
[0105] Pre & Post Challenge:120, 122, 124, 126, 128, 130, 132, 134
[0106] Serology: 0, 30, 60, 91, 105, 120, 134, 148
[0107] Post-vaccination viremia (vRNA) is dominated by DENVax-2. DENVax-4 vRNA detected in one animal from DENVax-HD+on day 8 post-vaccination. The trivalent DENVax-1,-2,-3 is more immunogenic and elicits a more balanced response than the DENVax-1,-3,-4 formulation. It is contemplated that the modified DEN-4 strains disclosed herein will improve this outcome. (See for example, FIG. 1).
TABLE-US-00001
[0107] TABLE 1 Preclinical evaluation of trivalent DENVax in non-human Route of Immunization & Challenge: Subcutaneous (0.5 mL) DENVax Formulation DENVax DENVax1 - 1.25 .times. 10.sup.4 Trivalent DENVax1 - 1.25 .times. 10.sup.4 Trivalent DENVax1 - 1.25 .times. 10.sup.4 HD+: DENVax2 - 6.04 .times. 10.sup.4 (DENVax1,2,3) DENVax2 - 6.04 .times. 10.sup.4 (DENVax1,3,4) DENVax3 - 1.30 .times. 10.sup.5 DENVax3 - 1.30 .times. 10.sup.5 DENVax3 - 1.30 .times. 10.sup.5 DENVax4 - 1.34 .times. 10.sup.6 DENVax4 - 1.34 .times. 10.sup.6
TABLE-US-00002 TABLE 2 Design: Treatment on Day 0 Challenge Group and 90 on day 120 Aim 1 DENVax HD+ Challenge Clinical dosing with DENV-2 and DENV-4 2 Trivalent Challenge Assess trivalent vaccine (DENVax1,2,3 - same with protection against titers as HD+) DENV-4 dengue virus serotypes (e.g. DEN-4) 3 Trivalent Challenge Assess trivalent (DENVax1,3,4 - same wit followed by monovalent titers as HD+) DENV-2 administration and assess protection against dengue virus serotypes (e.g. What is the neutralizing antibody level against DEN-2 using only a DEN-2 backbone for immunization) 4 FTA Challenge Challenge control group with DENV-2 and DENV-4 5 Trivalent formulation Challenge Challenge control group on Day 0 and a with monovalent DENV-2 and formulation on the DENV-4 same day or within 90 days of the Trivalent formulation (or reverse: monovalent first) DENVax 1, 2, 3; DENVax 2, 3, 4; DENVax1, 2, 4 or DENVax1, 3, 4 on a DEN-2 backbone 6 Trivalent formulation Challenge Challenge control group on Day 0 and a with monovalent DENV-2 and formulation on the DENV-4 same day in a different anatomical site; or within 90 days of the Trivalent formulation (or reverse: monovalent first) DENVax 1, 2, 3; DENVax 2, 3, 4; DENVax1, 2, 4 or DENVax1, 3, 4 on a DEN-2 backbone
[0108] This application contains a Sequence Listing submitted via EFS-web and is hereby incorporated by reference in its entirety. The ASCII copy, created on Dec.14, 2017, is named 20171214_478484.283_SequenceListing_ST25 and is 475 KB in size.
All of the COMPOSITIONS and METHODS disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods have been described in terms of preferred embodiments, it is apparent to those of skill in the art that variations maybe applied to the COMPOSITIONS and METHODS and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope herein. More specifically, certain agents that are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept as defined by the appended claims.
Sequence CWU
1
1
33129PRTArtificialDerived from Dengue virus serotype 2 (DENV-2) 1Asn Ile
Leu Asn Arg Arg Arg Arg Ser Ala Gly Met Ile Ile Met Leu 1 5
10 15 Ile Pro Thr Val Met Ala Phe
His Leu Thr Thr Arg Asn 20 25
229PRTArtificialDerived from Dengue virus serotype 4 (DENV-4 WT)
2Asn Ile Leu Asn Gly Arg Lys Arg Ser Thr Ile Thr Leu Leu Cys Leu 1
5 10 15 Ile Pro Thr Val
Met Ala Phe His Leu Ser Thr Arg Asp 20 25
329PRTArtificialDerived from Dengue virus seroptype 4
(DENVax-4ori) 3Asn Ile Leu Asn Arg Arg Arg Ser Ser Ala Gly Met Ile Ile
Met Leu 1 5 10 15
Ile Pro Thr Val Met Ala Phe His Leu Thr Thr Arg Asp 20
25 429PRTArtificialDerived from Dengue virus
serotype 4 (DENVax-4b) 4Asn Ile Leu Asn Arg Arg Arg Ser Ser Thr Ile
Thr Leu Leu Cys Leu 1 5 10
15 Ile Pro Thr Val Met Ala Phe His Leu Ser Thr Arg Asp
20 25 529PRTArtificialDerived from
Dengue virus serotype 4 (DENVax-4c) 5Asn Ile Leu Asn Gly Arg Lys Arg
Ser Thr Ile Thr Leu Leu Cys Leu 1 5 10
15 Ile Pro Thr Val Met Ala Phe His Leu Ser Thr Arg Asp
20 25
628PRTArtificialDerived from Dengue virus serotype 4 (DENVax-4d)
6Ile Leu Asn Gly Arg Lys Arg Ser Thr Ile Thr Leu Leu Cys Leu Ile 1
5 10 15 Pro Thr Val Met
Ala Phe His Leu Ser Thr Arg Asp 20 25
710722DNAArtificialDengue virus chimeric construct DENVax-4e
7agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaatgta
60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg
120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag
180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg
240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga
300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt
360ggaaggatgc tgaacatctt gaataggaga cgcagctcaa cgataacatt gctgtacttg
420attcccaccg taatggcgtt tcacttgtca acgcgtgatg gcgaacccct catgatagtg
480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat caacaaatgc
540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta taaatgcccc
600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac gtctacctgg
660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg ctcagtagct
720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat gtcatcggaa
780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc aggattcgcg
840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg aactgtcttc
900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg agtaggaaac
960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct agaacatgga
1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact gactaagaca
1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat atcaaacata
1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga acaagaccaa
1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg tggcttgttt
1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat aacaggcaat
1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa tggagacacc
1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac tcccaggtca
1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg tgaacccagg
1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac atggcttgtg
1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga cacatcagag
1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc caagagacag
1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc tggagccaca
1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg caaagtccgt
1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa gttctcaatt
1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa gtatgaaggt
1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga aaaagtggtt
1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac caacatagag
2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag tgcattaaca
2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac atacagaggt
2160gcaaaacgaa tggccattct aggtgaaaca gcttgggatt ttggttccgt tggtggactg
2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac aaccctgttt
2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg gattggcacg
2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt gacactgtat
2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa caaagaactg
2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga acaatacaag
2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca tgaagaggac
2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca aataacacca
2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac aggagacatc
2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga gctgaagtat
2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa ccagaccttt
2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg gaattcgttg
2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa attgaaagaa
2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga caacagagcc
3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg gaagatagag
3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac cctctggagc
3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc agtgtctcaa
3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct aggtaagctt
3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga ctgcggaaat
3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga atggtgctgc
3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg gtacgggatg
3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt cacagctgga
3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt cctggaggaa
3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt ttcttttgtg
3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt tatggtaggc
3660gccactatga cggatgacat aggtatgggc gtgacttatc ttgccctact agcagccttc
3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc caaggaattg
3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga gaccattctt
3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag aaatatggaa
3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc agtgatatta
3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc cccactgttc
4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat caaaggtctc
4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag gagctggcca
4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc tctcctaaaa
4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt gtgctacgtg
4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa atgggaagac
4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga agatggtagc
4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag aacaggattg
4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc atggtacctg
4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc cccacccatg
4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat tcttggatat
4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg gcatgtcaca
4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc ggacgtcaag
4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa ggaaggagaa
4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca aacgaaacct
4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt ttctcctgga
4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta tggtaatggt
4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa aagcattgaa
5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat catggacctc
5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga agctataaaa
5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga aatggaggaa
5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt gcacaccggg
5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct atcaccagtt
5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga cccagcaagt
5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc tgggattttt
5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc accaatcata
5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg ggtcacggat
5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga tatagcagct
5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt tgattctgag
5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat ttcagaaatg
5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa accagtcata
5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac ccactctagt
5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga ccagtacata
5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga agctaaaatg
6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga accagagcgt
6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag gaaaaccttt
6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt ggcagctgaa
6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa ccaaatccta
6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa attgaaaccc
6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt taaggaattt
6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag gctcccaacc
6420ttcatgactc agaaggcaag agacgcactg gacaacttag cagtgctgca cacggctgag
6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct ggagacattg
6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt gatgagcgca
6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag catcctccta
6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga gttttttctc
6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa ccaactgacc
6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga gatgggtttc
6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca acccgagagc
6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc cgtggccaca
6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa tgtgtcccta
7020acagctatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg gccattgtca
7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt caaccccata
7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg gccaggactc
7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat gaaaaaccca
7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc aaagtttgaa
7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt gatgatgagg
7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc cacattgtgg
7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc taacattttt
7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa cacaaccaac
7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa aagccgattg
7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca ggaagtggat
7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc tgtgtcgcga
7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga agggaaagta
7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact aaagaatgta
7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat ccccatgtca
7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt catcccgcca
7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc cacagtggaa
8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa caacactcaa
8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat ggaagcacta
8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc cacacatgag
8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat gatttcaagg
8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc ggatgttgac
8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct agatataatt
8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta tgaccaagac
8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac tggatcagca
8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt cgtccccatg
8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt ttttaaagag
8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat gaaaataaca
8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg caccagagaa
8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac tgatgagaac
8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct ggttgacaag
8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat gatgggaaaa
8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat atggtacatg
9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga agatcactgg
9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa gctaggttac
9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga caccgcagga
9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac aaaccacatg
9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca aaacaaggtg
9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc gagaagagac
9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa tatggaagcc
9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca cctaacaatc
9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag gttatcaaga
9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt cgcaagcgct
9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg ggaaccttca
9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca tgagttaatc
9720atgaaagacg gtcgcgtact cgttgttcca tgtagaaacc aagatgaact gattggcaga
9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt ggggaagtct
9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct ggcggcaaat
9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac ctggtccata
9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa cagggtgtgg
10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga ggaaatccca
10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac aagcagggcc
10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat aggcaatgaa
10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga agaagcagga
10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt cggattaagc
10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta aaagaagtca
10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca cctgagaagg
10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta gtggactagc
10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa ggcgagatga
10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa caaaaaacag
10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat tccaggcaca
10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tc
10722810722DNAArtificialDengue virus chimeric construct DENVax-4h
8agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaatgta
60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg
120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag
180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg
240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga
300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt
360ggaaggatgc tgaacatctt gaataggaga cgcagctctg caggcatgat cattatgctg
420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gcgaacccct catgatagtg
480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat caacaaatgc
540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta taaatgcccc
600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac gtctacctgg
660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg ctcagtagct
720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat gtcatcggaa
780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc aggattcgcg
840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg aactgtcttc
900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg agtaggaaac
960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct agaacatgga
1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact gactaagaca
1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat atcaaacata
1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga acaagaccaa
1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg tggcttgttt
1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat aacaggcaat
1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa tggagacacc
1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac tcccaggtca
1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg tgaacccagg
1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac atggcttgtg
1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga cacatcagag
1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc caagagacag
1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc tggagccaca
1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg caaagtccgt
1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa gttctcaatt
1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa gtatgaaggt
1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga aaaagtggtt
1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac caacatagag
2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag tgcattaaca
2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac atacagaggt
2160gcaaaacgaa tggccattct aggtaaaaca gcttgggatt ttggttccgt tggtggactg
2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac aaccctgttt
2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg gattggcacg
2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt gacactgtat
2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa caaagaactg
2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga acaatacaag
2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca tgaagaggac
2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca aataacacca
2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac aggagacatc
2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga gctgaagtat
2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa ccagaccttt
2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg gaattcgttg
2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa attgaaagaa
2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga caacagagcc
3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg gaagatagag
3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac cctctggagc
3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc agtgtctcaa
3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct aggtaagctt
3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga ctgcggaaat
3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga atggtgctgc
3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg gtacgggatg
3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt cacagctgga
3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt cctggaggaa
3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt ttcttttgtg
3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt tatggtaggc
3660gccactatga cggatgacat aggtatgggc gtgacttatc ttgccctact agcagccttc
3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc caaggaattg
3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga gaccattctt
3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag aaatatggaa
3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc agtgatatta
3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc cccactgttc
4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat caaaggtctc
4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag gagctggcca
4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc tctcctaaaa
4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt gtgctacgtg
4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa atgggaagac
4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga agatggtagc
4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag aacaggattg
4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc atggtacctg
4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc cccacccatg
4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat tcttggatat
4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg gcatgtcaca
4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc ggacgtcaag
4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa ggaaggagaa
4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca aacgaaacct
4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt ttctcctgga
4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta tggtaatggt
4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa aagcattgaa
5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat catggacctc
5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga agctataaaa
5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga aatggaggaa
5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt gcacaccggg
5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct atcaccagtt
5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga cccagcaagt
5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc tgggattttt
5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc accaatcata
5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg ggtcacggat
5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga tatagcagct
5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt tgattctgag
5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat ttcagaaatg
5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa accagtcata
5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac ccactctagt
5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga ccagtacata
5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga agctaaaatg
6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga accagagcgt
6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag gaaaaccttt
6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt ggcagctgaa
6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa ccaaatccta
6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa attgaaaccc
6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt taaggaattt
6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag gctcccaacc
6420ttcatgactc agaaggcaag agacgcactg gacaacttag cagtgctgca cacggctgag
6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct ggagacattg
6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt gatgagcgca
6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag catcctccta
6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga gttttttctc
6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa ccaactgacc
6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga gatgggtttc
6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca acccgagagc
6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc cgtggccaca
6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa tgtgtcccta
7020acagctatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg gccattgtca
7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt caaccccata
7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg gccaggactc
7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat gaaaaaccca
7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc aaagtttgaa
7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt gatgatgagg
7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc cacattgtgg
7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc taacattttt
7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa cacaaccaac
7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa aagccgattg
7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca ggaagtggat
7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc tgtgtcgcga
7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga agggaaagta
7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact aaagaatgta
7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat ccccatgtca
7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt catcccgcca
7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc cacagtggaa
8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa caacactcaa
8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat ggaagcacta
8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc cacacatgag
8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat gatttcaagg
8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc ggatgttgac
8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct agatataatt
8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta tgaccaagac
8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac tggatcagca
8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt cgtccccatg
8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt ttttaaagag
8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat gaaaataaca
8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg caccagagaa
8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac tgatgagaac
8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct ggttgacaag
8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat gatgggaaaa
8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat atggtacatg
9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga agatcactgg
9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa gctaggttac
9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga caccgcagga
9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac aaaccacatg
9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca aaacaaggtg
9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc gagaagagac
9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa tatggaagcc
9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca cctaacaatc
9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag gttatcaaga
9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt cgcaagcgct
9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg ggaaccttca
9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca tgagttaatc
9720atgaaagacg gtcgcgtact cgttgttcca tgtagaaacc aagatgaact gattggcaga
9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt ggggaagtct
9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct ggcggcaaat
9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac ctggtccata
9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa cagggtgtgg
10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga ggaaatccca
10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac aagcagggcc
10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat aggcaatgaa
10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga agaagcagga
10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt cggattaagc
10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta aaagaagtca
10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca cctgagaagg
10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta gtggactagc
10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa ggcgagatga
10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa caaaaaacag
10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat tccaggcaca
10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tc
10722910722DNAArtificialDengue virus chimeric construct DENVax-4i
9agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaatgta
60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg
120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag
180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg
240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga
300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt
360ggaaggatgc tgaacatctt gaataggaga cgcagctctg caggcatgat cattatgctg
420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gcgaacccct catgatagtg
480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat caacaaatgc
540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta taaatgcccc
600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac gtctacctgg
660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg ctcagtagct
720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat gtcatcggaa
780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc aggattcgcg
840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg aactgtcttc
900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg agtaggaaac
960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct agaacatgga
1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact gactaagaca
1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat atcaaacata
1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga acaagaccaa
1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg tggcttgttt
1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat aacaggcaat
1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa tggagacacc
1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac tcccaggtca
1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg tgaacccagg
1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac atggcttgtg
1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga cacatcagag
1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc caagagacag
1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc tggagccaca
1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg caaagtccgt
1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa gttctcaatt
1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa gtatgaaggt
1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga aaaagtggtt
1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac caacatagag
2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag tgcattaaca
2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac atacagaggt
2160gcaaaacgaa tggccattct aggtgaaaca gcttgggatt ttggttccgt tggtggactg
2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac aaccctgttt
2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg gattggcacg
2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt gacactgtat
2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa caaagaactg
2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga acaatacaag
2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca tgaagaggac
2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca aataacacca
2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac aggagacatc
2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga gctgaagtat
2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa ccagaccttt
2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg gaattcgttg
2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa attgaaagaa
2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga caacagagcc
3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg gaagatagag
3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac cctctggagc
3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc agtgtctcaa
3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct aggtaagctt
3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga ctgcggaaat
3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga atggtgctgc
3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg gtacgggatg
3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt cacagctgga
3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt cctggaggaa
3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt ttcttttgtg
3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt tatggtaggc
3660gccactatga cggatgacat aggtatgggc gtgacttatc ttgccctact agcagccttc
3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc caaggaattg
3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga gaccattctt
3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag aaatatggaa
3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc agtgatatta
3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc cccactgttc
4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat caaaggtctc
4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag gagctggcca
4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc tctcctaaaa
4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt gtgctacgtg
4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa atgggaagac
4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga agatggtagc
4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag aacaggattg
4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc atggtacctg
4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc cccacccatg
4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat tcttggatat
4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg gcatgtcaca
4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc ggacgtcaag
4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa ggaaggagaa
4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca aacgaaacct
4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt ttctcctgga
4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta tggtaatggt
4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa aagcattgaa
5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat catggacctc
5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga agctataaaa
5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga aatggaggaa
5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt gcacaccggg
5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct atcaccagtt
5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga cccagcaagt
5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc tgggattttt
5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc accaatcata
5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg ggtcacggat
5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga tatagcagct
5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt tgattctgag
5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat ttcagaaatg
5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa accagtcata
5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac ccactctagt
5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga ccagtacata
5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga agctaaaatg
6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga accagagcgt
6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag gaaaaccttt
6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt ggcagctgaa
6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa ccaaatccta
6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa attgaaaccc
6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt taaggaattt
6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag gctcccaacc
6420ttcttgactc agaaggcaag agacgcactg gacaacttag cagtgctgca cacggctgag
6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct ggagacattg
6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt gatgagcgca
6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag catcctccta
6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga gttttttctc
6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa ccaactgacc
6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga gatgggtttc
6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca acccgagagc
6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc cgtggccaca
6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa tgtgtcccta
7020acagctatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg gccattgtca
7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt caaccccata
7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg gccaggactc
7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat gaaaaaccca
7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc aaagtttgaa
7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt gatgatgagg
7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc cacattgtgg
7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc taacattttt
7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa cacaaccaac
7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa aagccgattg
7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca ggaagtggat
7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc tgtgtcgcga
7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga agggaaagta
7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact aaagaatgta
7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat ccccatgtca
7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt catcccgcca
7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc cacagtggaa
8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa caacactcaa
8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat ggaagcacta
8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc cacacatgag
8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat gatttcaagg
8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc ggatgttgac
8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct agatataatt
8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta tgaccaagac
8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac tggatcagca
8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt cgtccccatg
8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt ttttaaagag
8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat gaaaataaca
8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg caccagagaa
8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac tgatgagaac
8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct ggttgacaag
8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat gatgggaaaa
8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat atggtacatg
9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga agatcactgg
9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa gctaggttac
9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga caccgcagga
9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac aaaccacatg
9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca aaacaaggtg
9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc gagaagagac
9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa tatggaagcc
9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca cctaacaatc
9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag gttatcaaga
9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt cgcaagcgct
9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg ggaaccttca
9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca tgagttaatc
9720atgaaagacg gtcgcgtact cgttgttcca tgtagaaacc aagatgaact gattggcaga
9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt ggggaagtct
9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct ggcggcaaat
9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac ctggtccata
9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa cagggtgtgg
10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga ggaaatccca
10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac aagcagggcc
10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat aggcaatgaa
10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga agaagcagga
10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt cggattaagc
10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta aaagaagtca
10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca cctgagaagg
10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta gtggactagc
10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa ggcgagatga
10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa caaaaaacag
10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat tccaggcaca
10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tc
107221010699DNAArtificialSynthetic construct 10agttgttagt ctacgtggac
cgacaagaac agtttcgact cggaagcttg cttaacgtag 60tgctgacagt tttttattag
agagcagatc tctgatgaac aaccaacgga aaaagacggg 120aaaaccgtct atcaatatgc
tgaaacgcgt gagaaaccgt gtgtcaactg gatcacagtt 180ggcgaagaga ttctcaagag
gattgctgaa cggccaagga ccaatgaaat tggttatggc 240atttatagct ttcctcagat
ttctagccat tccaccgaca gcaggagtct tggctagatg 300gggtaccttt aagaagtcgg
gggctattaa ggtcttaaaa ggcttcaaga aggagatctc 360aaacatgctg agcattatca
acaaacggaa aaagacatcg ctctgtctca tgatgatgtt 420accagcaaca cttgctttcc
acttaacttc acgagatgga gagccgcgca tgattgtggg 480gaagaatgaa agaggaaaat
ccctactttt caagacagcc tctggaatca acatgtgcac 540actcatagcc atggatctgg
gagagatgtg tgatgacacg gtcacttaca aatgccccca 600cattaccgaa gtggagcctg
aagacattga ctgctggtgc aaccttacat cgacatgggt 660gacttatgga acatgcaatc
aagctggaga gcatagacgc gataagagat cagtggcgtt 720agctccccat gttggcatgg
gactggacac acgcactcaa acctggatgt cggctgaagg 780agcttggaga caagtcgaga
aggtagagac atgggccctt aggcacccag ggtttaccat 840actagcccta tttcttgccc
attacatagg cacttccttg acccagaaag tggttatttt 900tatactatta atgctggtta
ccccatccat gacaatgaga tgtgtaggag taggaaacag 960agattttgtg gaaggcctat
cgggagctac gtgggttgac gtggtgctcg agcacggtgg 1020gtgtgtgact accatggcta
agaacaagcc cacgctggac atagagcttc agaagaccga 1080ggccacccaa ctggcgaccc
taaggaagct atgcattgag ggaaaaatta ccaacataac 1140aaccgactca agatgtccca
cccaagggga agcgatttta cctgaggagc aggaccagaa 1200ctacgtgtgt aagcatacat
acgtggacag aggctgggga aacggttgtg gtttgtttgg 1260caagggaagc ttggtgacat
gcgcgaaatt tcaatgttta gaatcaatag agggaaaagt 1320ggtgcaacat gagaacctca
aatacaccgt catcatcaca gtgcacacag gagaccaaca 1380ccaggtggga aatgaaacgc
agggagtcac ggctgagata acaccccagg catcaaccgc 1440tgaagccatt ttacctgaat
atggaaccct cgggctagaa tgctcaccac ggacaggttt 1500ggatttcaat gaaatgatct
cattgacaat gaagaacaaa gcatggatgg tacatagaca 1560atggttcttt gacttacccc
taccatggac atcaggagct acagcagaaa caccaacttg 1620gaacaggaaa gagcttcttg
tgacatttaa aaatgcacat gcaaaaaagc aagaagtagt 1680tgttcttgga tcacaagagg
gagcaatgca tacagcactg acaggagcta cagagatcca 1740aacctcagga ggcacaagta
tctttgcggg gcacttaaaa tgtagactca agatggacaa 1800attggaactc aaggggatga
gctatgcaat gtgcttgagt agctttgtgt tgaagaaaga 1860agtctccgaa acgcagcatg
ggacaatact cattaaggtt gagtacaaag gggaagatgc 1920accctgcaag attcctttct
ccacggagga tggacaagga aaagctcaca atggcagact 1980gatcacagcc aatccagtgg
tgaccaagaa ggaggagcct gtcaacattg aggctgaacc 2040tccttttgga gaaagtaaca
tagtaattgg aattggagac aaagccctga aaatcaactg 2100gtacaagaag ggaagctcga
ttgggaagat gttcgaggcc actgccagag gtgcaaggcg 2160catggccatc ttgggagaca
cagcctggga ctttggatca gtgggtggtg ttttgaattc 2220attagggaaa atggtccacc
aaatatttgg gagtgcttac acagccctat ttggtggagt 2280ctcctggatg atgaaaattg
gaataggtgt cctcttaacc tggatagggt tgaactcaaa 2340aaatacttct atgtcatttt
catgcatcgc gataggaatc attacactct atctgggagc 2400cgtggtgcaa gctgacatgg
ggtgtgtcat aaactggaaa ggcaaagaac tcaaatgtgg 2460aagtggaatt ttcgtcacta
atgaggtcca cacctggaca gagcaataca aatttcaagc 2520agactccccc aagagactgg
caacagccat tgcaggcgct tgggaaaatg gagtgtgcgg 2580aattaggtca acaaccagaa
tggagaacct cttgtggaag caaatagcca atgaactgaa 2640ttacatatta tgggaaaaca
acattaaatt aacggtagtt gtaggcgaca taactggggt 2700cttagagcaa gggaaaagaa
cactaacacc acaacccatg gagctaaaat attcttggaa 2760aacatgggga aaggcaaaaa
tagtgacagc tgaaacacaa aattcctctt tcataataga 2820tgggccaagc acaccggagt
gtccaagtgc ctcaagagca tggaatgtgt gggaggtgga 2880ggattacggg ttcggagttt
tcacaaccaa catatggctg aaactccgag aggtgtacac 2940ccaactatgt gaccataggc
taatgtcggc agccgtcaag gatgagaggg ctgtacatgc 3000cgacatgggc tattggatag
aaagccaaaa gaatgggagt tggaagctag aaaaagcatc 3060cttcatagag gtgaaaacct
gcacatggcc aaaatcacac actctctgga gcaatggtgt 3120gctagagagt gacatgatta
tcccaaagag tctagctggt cccatttcgc aacacaacca 3180caggcccggg taccacaccc
aaacggcagg accctggcac ttaggaaaat tggagctgga 3240cttcaactat tgtgaaggaa
caacagttgt catctcagaa aactgtggga caagaggccc 3300atcattgaga acaacaacgg
tgtcagggaa gttgatacac gaatggtgct gccgctcgtg 3360cacacttcct cccctacgat
acatgggaga agacggctgc tggtatggca tggaaatcag 3420acccattaat gagaaagaag
agaatatggt aaagtctcta gcctcagcag ggagtggaaa 3480ggtggacaac ttcacaatgg
gtgtcttgtg tttggcaatc ctctttgaag aggtgatgag 3540aggaaaattt gggaaaaaac
acatgattgc aggggttctc ttcacgtttg tgctcctcct 3600ctcagggcaa ataacatgga
gagacatggc gcacacactc ataatgattg ggtccaacgc 3660ctctgacaga atggggatgg
gcgtcactta cctagctcta attgcaacat ttaaaattca 3720gccattcctg gctttgggat
tcttcctgag gaaactgaca tctagagaaa atttattgct 3780gggagttggg ttggccatgg
cagcaacgtt acgactgcca gaggacattg aacagatggc 3840gaatggaatt gctttggggc
tcatggctct taaactgata acacaatttg aaacatacca 3900actatggacg gcattagttt
ccctaacgtg ttcaaataca attttcacgt tgactgttgc 3960ctggagaaca gccactctga
ttttagccgg aatttcgctt ttgccagtgt gccagtcttc 4020gagcatgagg aaaacagatt
ggctcccaat gactgtggca gctatgggag ctcaacccct 4080accacttttt attttcagtc
tgaaagatac actcaaaagg agaagctggc cactgaatga 4140gggggtgatg gcagttggac
ttgtgagcat tctagctagt tctctcctta ggaatgatgt 4200gcctatggct ggaccattag
tggctggggg cttgctgata gcgtgctacg tcataactgg 4260cacgtcagca gacctcactg
tagaaaaagc agcagatgta acatgggagg aagaggccga 4320gcaaacagga gtgtcccaca
atttaatggt cacagttgat gatgatggaa caatgagaat 4380aaaagatgac gagactgaga
acatcttaac agtgctttta aaaacagcac tactaatagt 4440atcaggcatc tttccatact
ccatacccgc aacactgttg gtctggcata cttggcaaaa 4500gcaaacccaa agatccggcg
tcctatggga cgtacccagc cccccagaga cacagaaagc 4560ggaactggaa gaaggggtct
ataggatcaa acagcaagga atttttggga aaacccaagt 4620gggggttgga gtacagaaag
aaggagtttt ccacaccatg tggcatgtca caagaggggc 4680agtgttgaca cacaatggga
aaagactgga accaaactgg gctagcgtga aaaaagatct 4740gatttcatac ggaggaggat
ggagattgag tgcacaatgg caaaaggggg aggaggtgca 4800ggttattgcc gtagagcctg
ggaagaaccc aaagaacttt caaaccatgc caggcatttt 4860tcagacaaca acaggggaaa
taggagcaat tgcactggat ttcaagcctg gaacttcagg 4920atctcccatc ataaacagag
agggaaaggt agtgggactg tatggcaatg gagtggttac 4980aaagaatgga ggctatgtca
gtggaatagc gcaaacaaat gcagaaccag atggaccgac 5040accagagttg gaagaagaga
tgttcaaaaa gcgaaatcta accataatgg atctccatcc 5100tgggtcagga aagacgcgga
aatatcttcc agctattgtt agagaggcaa tcaagagacg 5160cttaaggact ctaattttgg
caccaacaag ggtagttgca gctgagatgg aagaagcatt 5220gaaagggctc ccaataaggt
atcaaacaac tgcaacaaaa tctgaacaca caggaagaga 5280gattgttgat ctaatgtgtc
acgcaacgtt cacaatgcgc ttgctgtcac cagtcagggt 5340tccaaactac aacttgataa
taatggatga ggcccatttc acagacccag ccagtatagc 5400ggctagaggg tacatatcaa
ctcgtgtagg aatgggagag gcagccgcaa ttttcatgac 5460agcaacaccc cctggaacag
ctgatgcctt tcctcagagc aacgctccaa ttcaagatga 5520agagagagac ataccggaac
gctcatggaa ttcaggcaat gaatggatta ctgactttgt 5580tgggaagaca gtgtggtttg
tccctagcat caaagccgga aatgacatag caaactgctt 5640gcggaaaaat ggaaaaaagg
ttattcaact cagcaggaag acctttgaca cagaatatca 5700aaagaccaaa ctgaatgatt
gggactttgt ggtgacaaca gacatttcag aaatgggagc 5760caatttcaaa gcagatagag
tgatcgaccc aagaagatgt ctcaagccgg tgattttgac 5820agatggaccc gagcgggtga
tcctggctgg accaatgcca gtcaccgtag cgagcgctgc 5880gcaaaggaga gggagagttg
gcaggaaccc acaaaaagaa aatgaccagt acatattcat 5940gggccagcct ctcaacaatg
atgaagacca tgctcactgg acagaagcaa aaatgctgct 6000ggacaacatc aacacaccag
aagggattat accagctctc tttgaaccag aaagggagaa 6060gtcagccgcc atagacggcg
aataccgcct gaagggtgag tccaggaaga ctttcgtgga 6120actcatgagg aggggtgacc
tcccagtttg gctagcccat aaagtagcat cagaagggat 6180caaatataca gatagaaaat
ggtgctttga tggagaacgt aataatcaaa ttttagagga 6240gaatatggat gtggaaatct
ggacaaagga aggagaaaag aaaaaactga gacctaggtg 6300gcttgatgcc cgcacttatt
cagatccttt agcactcaaa gaattcaagg attttgcagc 6360tggcagaaag tcaatcgccc
ttgatcttgt gacagaaata ggaagagtgc cttcacactt 6420agcccacaga acgagaaacg
ccctggataa tttggtgatg ctgcacacgt cagaacatgg 6480cggtagggcc tacaggcatg
cagtggagga actaccagaa acgatggaaa cactcttact 6540cctgggactg atgatcttgt
taacaggtgg agcaatgctc ttcttgatat caggtaaagg 6600gattggaaag acttcaatag
gactcatttg tgtaattgct tccagcggca tgttatggat 6660ggctgatgtc ccactccaat
ggatcgcatc ggctatagtc ctggagtttt ttatgatggt 6720gttgctcata ccagaaccag
aaaagcagag aactccccaa gacaaccaac tcgcatatgt 6780cgtgataggc atacttacat
tggctgcaat agtagcggcc aatgaaatgg gactgttgga 6840aactacaaag agagatttag
gaatgtctaa agaaccaggt gttgtttctc caaccagcta 6900tttggatgtg gacttgcacc
cagcatcagc ctggacattg tacgccgtgg ccacaacagt 6960aataacacca atgttgagac
acaccataga gaattccaca gcaaatgtgt ctctggcagc 7020catagctaac caggcagtgg
tcctgatggg tttagacaaa ggatggccga tatcgaaaat 7080ggacttgggc gtaccactat
tggcactggg ttgctattca caagtgaacc cactaactct 7140tgcagcggca gtacttttgc
tagtcacaca ttatgcaatt ataggtccag gattgcaggc 7200aaaagccacc cgtgaagctc
agaaaaggac agctgctgga ataatgaaga atccaacggt 7260ggatggaata atgacaatag
acctagatcc tgtaatatat gattcaaaat ttgaaaagca 7320actaggacag gtcatgctcc
tggttctgtg tgcagtccaa cttttattga tgagaacatc 7380atgggccttg tgtgaagttc
taaccctagc cacaggacca ataacaacac tctgggaagg 7440atcacctggg aagttctgga
acaccacgat agctgtttcc atggcgaaca tctttagagg 7500gagctattta gcaggagctg
ggcttgcttt ttctatcatg aaatcagttg gaacaggaaa 7560gagaggaaca gggtcacaag
gtgaaacctt aggagaaaag tggaaaaaga aattaaatca 7620gttatcccgg aaagagtttg
acctttacaa gaaatccgga atcaccgaag tggatagaac 7680agaagccaaa gaagggttaa
aaagaggaga aataacacac catgccgtgt ccagaggcag 7740cgcaaaactt caatggttcg
tggagagaaa catggtcatt cctgaaggaa gagtcataga 7800cctaggctgt ggaagaggag
gctggtcata ttactgtgca ggactgaaaa aagttacaga 7860agtgcgagga tacacaaaag
gcggcccagg acacgaagaa ccagtaccta tgtctacata 7920cggatggaac atagtcaagt
taatgagtgg aaaggatgtt ttttatctgc cacctgaaaa 7980gtgtgatacc ctattgtgtg
acattggaga atcttcacca agcccaacag tggaagaaag 8040cagaaccata agagttttga
agatggttga accatggcta aagaacaacc agttttgcat 8100taaagtattg aacccataca
tgccaactgt gattgagcac ttagaaagac tacaaaggaa 8160acatggagga atgcttgtga
gaaatccact ctcacgaaac tccacgcacg aaatgtattg 8220gatatccaat ggtacaggca
atatcgtctc ttcagtcaac atggtatcca gattgctact 8280gaacagattc acaatgacac
acaggagacc caccatagag aaagatgtgg atctaggagc 8340aggaacccga catgtcaatg
cggaaccaga aacacccaac atggatgtca ttggggaaag 8400aataaaaagg atcaaagagg
agcatagttc aacatggcac tatgatgatg aaaatcctta 8460caaaacgtgg gcttaccatg
gatcctatga agtaaaagcc acaggctcag cctcctccat 8520gataaatgga gtcgtgaaac
tcctcacaaa accatgggat gtggtgccca tggtgacaca 8580gatggcaatg acagatacaa
ctccattcgg ccagcaaaga gtttttaaag agaaagtgga 8640caccaggaca cctaggccca
tgccaggaac aagaaaggtt atggagatca cagcggagtg 8700gctttggagg accctgggaa
ggaacaaaag acccagatta tgcacaaggg aggaattcac 8760aaagaaggtc agaaccaacg
cagctatggg cgctgtcttc acagaagaga accaatggga 8820cagtgcgaga gctgctgttg
aggacgaaga attttggaaa cttgtggaca gagaacgtga 8880actccacaaa ctgggcaagt
gtggaagctg cgtttacaac atgatgggca agagagagaa 8940aaaacttgga gagtttggta
aagcaaaagg cagtagggct atatggtaca tgtggttggg 9000agccaggtac cttgagttcg
aggcgctcgg attcctcaat gaagaccact ggttctcgcg 9060tgaaaactct tacagtggag
tagaaggaga aggactgcac aagctgggat acatcttgag 9120agatatttcc aagatacccg
gaggagccat gtatgctgat gacacagccg gttgggacac 9180aagaataaca gaagatgacc
tgcacaatga ggaaaaaatc acacagcaga tggaccctga 9240acacaggcag ctagcgaacg
ctatattcaa gctcacatac caaaacaaag tggtcaaagt 9300ccaacgacca actccaaagg
gcacggtaat ggacatcata tctaggaaag accaaagagg 9360cagtggacag gtgggaactt
atggtctgaa cacattcacc aacatggaag cccagctaat 9420cagacaaatg gaaggagaag
gcgtgttgtc aaaggcagac ctcgagaacc cccatccgct 9480agagaagaaa attacacaat
ggttggaaac taaaggagtg gaaaggttaa aaagaatggc 9540catcagcggg gatgattgcg
ttgtgaaacc aatcgacgac agattcgcca atgccctgct 9600tgccctgaac gatatgggaa
aggttagaaa ggacatacct caatggcagc catcaaaggg 9660atggcatgat tggcaacagg
tccccttctg ctcccaccac tttcatgaat tgatcatgaa 9720agatggaaga aagttggtag
ttccctgcag accccaggac gaactaatag gaagagcgag 9780aatctcccaa ggagcaggat
ggagccttag agaaactgca tgtctaggga aagcctacgc 9840tcaaatgtgg gctctcatgt
attttcacag aagagatctt agactagcat ccaacgccat 9900atgttcagca gtaccagtcc
actgggtccc cacgagcaga acgacatggt ctattcatgc 9960tcaccatcag tggatgacta
cagaagacat gcttactgtc tggaacaggg tgtggataga 10020ggacaatcca tggatggaag
acaaaactcc agtcacaacg tgggaagatg ttccatatct 10080agggaagaga gaagaccaat
ggtgcggatc actcataggt ctcacttcca gagcaacctg 10140ggcccagaac atactcacag
caatccaaca ggtgagaagc ctcataggca atgaagagtt 10200tctggactac atgccttcga
tgaagagatt caggaaggag gaggagtcag agggagccat 10260ttggtaaaag caggaggtaa
actgtcaggc cacattaagc cacagtacgg aagaagctgt 10320gcagcctgtg agccccgtcc
aaggacgtta aaagaagaag tcaggcccaa aagccacggt 10380ttgagcaaac cgtgctgcct
gtagctccgt cgtggggacg taaagcctgg gaggctgcaa 10440accgtggaag ctgtacgcac
ggtgtagcag actagtggtt agaggagacc cctcccatga 10500cacaacgcag cagcggggcc
cgagcactga gggaagctgt acctccttgc aaaggactag 10560aggttagagg agaccccccg
caaacaaaaa cagcatattg acgctgggag agaccagaga 10620tcctgctgtc tcctcagcat
cattccaggc acagaacgcc agaaaatgga atggtgctgt 10680tgaatcaaca ggttctagt
10699113390PRTArtificialSynthetic construct 11Met Asn Asn Gln Arg Lys Lys
Thr Gly Lys Pro Ser Ile Asn Met Leu 1 5
10 15 Lys Arg Val Arg Asn Arg Val Ser Thr Gly Ser
Gln Leu Ala Lys Arg 20 25
30 Phe Ser Arg Gly Leu Leu Asn Gly Gln Gly Pro Met Lys Leu Val
Met 35 40 45 Ala
Phe Ile Ala Phe Leu Arg Phe Leu Ala Ile Pro Pro Thr Ala Gly 50
55 60 Val Leu Ala Arg Trp Gly
Thr Phe Lys Lys Ser Gly Ala Ile Lys Val 65 70
75 80 Leu Lys Gly Phe Lys Lys Glu Ile Ser Asn Met
Leu Ser Ile Ile Asn 85 90
95 Lys Arg Lys Lys Thr Ser Leu Cys Leu Met Met Met Leu Pro Ala Thr
100 105 110 Leu Ala
Phe His Leu Thr Ser Arg Asp Gly Glu Pro Arg Met Ile Val 115
120 125 Gly Lys Asn Glu Arg Gly Lys
Ser Leu Leu Phe Lys Thr Ala Ser Gly 130 135
140 Ile Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly
Glu Met Cys Asp 145 150 155
160 Asp Thr Val Thr Tyr Lys Cys Pro His Ile Thr Glu Val Glu Pro Glu
165 170 175 Asp Ile Asp
Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Thr Tyr Gly 180
185 190 Thr Cys Asn Gln Ala Gly Glu His
Arg Arg Asp Lys Arg Ser Val Ala 195 200
205 Leu Ala Pro His Val Gly Met Gly Leu Asp Thr Arg Thr
Gln Thr Trp 210 215 220
Met Ser Ala Glu Gly Ala Trp Arg Gln Val Glu Lys Val Glu Thr Trp 225
230 235 240 Ala Leu Arg His
Pro Gly Phe Thr Ile Leu Ala Leu Phe Leu Ala His 245
250 255 Tyr Ile Gly Thr Ser Leu Thr Gln Lys
Val Val Ile Phe Ile Leu Leu 260 265
270 Met Leu Val Thr Pro Ser Met Thr Met Arg Cys Val Gly Val
Gly Asn 275 280 285
Arg Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val Asp Val Val 290
295 300 Leu Glu His Gly Gly
Cys Val Thr Thr Met Ala Lys Asn Lys Pro Thr 305 310
315 320 Leu Asp Ile Glu Leu Gln Lys Thr Glu Ala
Thr Gln Leu Ala Thr Leu 325 330
335 Arg Lys Leu Cys Ile Glu Gly Lys Ile Thr Asn Ile Thr Thr Asp
Ser 340 345 350 Arg
Cys Pro Thr Gln Gly Glu Ala Ile Leu Pro Glu Glu Gln Asp Gln 355
360 365 Asn Tyr Val Cys Lys His
Thr Tyr Val Asp Arg Gly Trp Gly Asn Gly 370 375
380 Cys Gly Leu Phe Gly Lys Gly Ser Leu Val Thr
Cys Ala Lys Phe Gln 385 390 395
400 Cys Leu Glu Ser Ile Glu Gly Lys Val Val Gln His Glu Asn Leu Lys
405 410 415 Tyr Thr
Val Ile Ile Thr Val His Thr Gly Asp Gln His Gln Val Gly 420
425 430 Asn Glu Thr Gln Gly Val Thr
Ala Glu Ile Thr Pro Gln Ala Ser Thr 435 440
445 Ala Glu Ala Ile Leu Pro Glu Tyr Gly Thr Leu Gly
Leu Glu Cys Ser 450 455 460
Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Ile Ser Leu Thr Met Lys 465
470 475 480 Asn Lys Ala
Trp Met Val His Arg Gln Trp Phe Phe Asp Leu Pro Leu 485
490 495 Pro Trp Thr Ser Gly Ala Thr Ala
Glu Thr Pro Thr Trp Asn Arg Lys 500 505
510 Glu Leu Leu Val Thr Phe Lys Asn Ala His Ala Lys Lys
Gln Glu Val 515 520 525
Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu Thr Gly 530
535 540 Ala Thr Glu Ile
Gln Thr Ser Gly Gly Thr Ser Ile Phe Ala Gly His 545 550
555 560 Leu Lys Cys Arg Leu Lys Met Asp Lys
Leu Glu Leu Lys Gly Met Ser 565 570
575 Tyr Ala Met Cys Leu Ser Ser Phe Val Leu Lys Lys Glu Val
Ser Glu 580 585 590
Thr Gln His Gly Thr Ile Leu Ile Lys Val Glu Tyr Lys Gly Glu Asp
595 600 605 Ala Pro Cys Lys
Ile Pro Phe Ser Thr Glu Asp Gly Gln Gly Lys Ala 610
615 620 His Asn Gly Arg Leu Ile Thr Ala
Asn Pro Val Val Thr Lys Lys Glu 625 630
635 640 Glu Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly
Glu Ser Asn Ile 645 650
655 Val Ile Gly Ile Gly Asp Lys Ala Leu Lys Ile Asn Trp Tyr Lys Lys
660 665 670 Gly Ser Ser
Ile Gly Lys Met Phe Glu Ala Thr Ala Arg Gly Ala Arg 675
680 685 Arg Met Ala Ile Leu Gly Asp Thr
Ala Trp Asp Phe Gly Ser Val Gly 690 695
700 Gly Val Leu Asn Ser Leu Gly Lys Met Val His Gln Ile
Phe Gly Ser 705 710 715
720 Ala Tyr Thr Ala Leu Phe Gly Gly Val Ser Trp Met Met Lys Ile Gly
725 730 735 Ile Gly Val Leu
Leu Thr Trp Ile Gly Leu Asn Ser Lys Asn Thr Ser 740
745 750 Met Ser Phe Ser Cys Ile Ala Ile Gly
Ile Ile Thr Leu Tyr Leu Gly 755 760
765 Ala Val Val Gln Ala Asp Met Gly Cys Val Ile Asn Trp Lys
Gly Lys 770 775 780
Glu Leu Lys Cys Gly Ser Gly Ile Phe Val Thr Asn Glu Val His Thr 785
790 795 800 Trp Thr Glu Gln Tyr
Lys Phe Gln Ala Asp Ser Pro Lys Arg Leu Ala 805
810 815 Thr Ala Ile Ala Gly Ala Trp Glu Asn Gly
Val Cys Gly Ile Arg Ser 820 825
830 Thr Thr Arg Met Glu Asn Leu Leu Trp Lys Gln Ile Ala Asn Glu
Leu 835 840 845 Asn
Tyr Ile Leu Trp Glu Asn Asn Ile Lys Leu Thr Val Val Val Gly 850
855 860 Asp Ile Thr Gly Val Leu
Glu Gln Gly Lys Arg Thr Leu Thr Pro Gln 865 870
875 880 Pro Met Glu Leu Lys Tyr Ser Trp Lys Thr Trp
Gly Lys Ala Lys Ile 885 890
895 Val Thr Ala Glu Thr Gln Asn Ser Ser Phe Ile Ile Asp Gly Pro Ser
900 905 910 Thr Pro
Glu Cys Pro Ser Ala Ser Arg Ala Trp Asn Val Trp Glu Val 915
920 925 Glu Asp Tyr Gly Phe Gly Val
Phe Thr Thr Asn Ile Trp Leu Lys Leu 930 935
940 Arg Glu Val Tyr Thr Gln Leu Cys Asp His Arg Leu
Met Ser Ala Ala 945 950 955
960 Val Lys Asp Glu Arg Ala Val His Ala Asp Met Gly Tyr Trp Ile Glu
965 970 975 Ser Gln Lys
Asn Gly Ser Trp Lys Leu Glu Lys Ala Ser Phe Ile Glu 980
985 990 Val Lys Thr Cys Thr Trp Pro Lys
Ser His Thr Leu Trp Ser Asn Gly 995 1000
1005 Val Leu Glu Ser Asp Met Ile Ile Pro Lys Ser
Leu Ala Gly Pro 1010 1015 1020
Ile Ser Gln His Asn His Arg Pro Gly Tyr His Thr Gln Thr Ala
1025 1030 1035 Gly Pro Trp
His Leu Gly Lys Leu Glu Leu Asp Phe Asn Tyr Cys 1040
1045 1050 Glu Gly Thr Thr Val Val Ile Ser
Glu Asn Cys Gly Thr Arg Gly 1055 1060
1065 Pro Ser Leu Arg Thr Thr Thr Val Ser Gly Lys Leu Ile
His Glu 1070 1075 1080
Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr Met Gly 1085
1090 1095 Glu Asp Gly Cys Trp
Tyr Gly Met Glu Ile Arg Pro Ile Asn Glu 1100 1105
1110 Lys Glu Glu Asn Met Val Lys Ser Leu Ala
Ser Ala Gly Ser Gly 1115 1120 1125
Lys Val Asp Asn Phe Thr Met Gly Val Leu Cys Leu Ala Ile Leu
1130 1135 1140 Phe Glu
Glu Val Met Arg Gly Lys Phe Gly Lys Lys His Met Ile 1145
1150 1155 Ala Gly Val Leu Phe Thr Phe
Val Leu Leu Leu Ser Gly Gln Ile 1160 1165
1170 Thr Trp Arg Asp Met Ala His Thr Leu Ile Met Ile
Gly Ser Asn 1175 1180 1185
Ala Ser Asp Arg Met Gly Met Gly Val Thr Tyr Leu Ala Leu Ile 1190
1195 1200 Ala Thr Phe Lys Ile
Gln Pro Phe Leu Ala Leu Gly Phe Phe Leu 1205 1210
1215 Arg Lys Leu Thr Ser Arg Glu Asn Leu Leu
Leu Gly Val Gly Leu 1220 1225 1230
Ala Met Ala Ala Thr Leu Arg Leu Pro Glu Asp Ile Glu Gln Met
1235 1240 1245 Ala Asn
Gly Ile Ala Leu Gly Leu Met Ala Leu Lys Leu Ile Thr 1250
1255 1260 Gln Phe Glu Thr Tyr Gln Leu
Trp Thr Ala Leu Val Ser Leu Thr 1265 1270
1275 Cys Ser Asn Thr Ile Phe Thr Leu Thr Val Ala Trp
Arg Thr Ala 1280 1285 1290
Thr Leu Ile Leu Ala Gly Ile Ser Leu Leu Pro Val Cys Gln Ser 1295
1300 1305 Ser Ser Met Arg Lys
Thr Asp Trp Leu Pro Met Thr Val Ala Ala 1310 1315
1320 Met Gly Ala Gln Pro Leu Pro Leu Phe Ile
Phe Ser Leu Lys Asp 1325 1330 1335
Thr Leu Lys Arg Arg Ser Trp Pro Leu Asn Glu Gly Val Met Ala
1340 1345 1350 Val Gly
Leu Val Ser Ile Leu Ala Ser Ser Leu Leu Arg Asn Asp 1355
1360 1365 Val Pro Met Ala Gly Pro Leu
Val Ala Gly Gly Leu Leu Ile Ala 1370 1375
1380 Cys Tyr Val Ile Thr Gly Thr Ser Ala Asp Leu Thr
Val Glu Lys 1385 1390 1395
Ala Ala Asp Val Thr Trp Glu Glu Glu Ala Glu Gln Thr Gly Val 1400
1405 1410 Ser His Asn Leu Met
Val Thr Val Asp Asp Asp Gly Thr Met Arg 1415 1420
1425 Ile Lys Asp Asp Glu Thr Glu Asn Ile Leu
Thr Val Leu Leu Lys 1430 1435 1440
Thr Ala Leu Leu Ile Val Ser Gly Ile Phe Pro Tyr Ser Ile Pro
1445 1450 1455 Ala Thr
Leu Leu Val Trp His Thr Trp Gln Lys Gln Thr Gln Arg 1460
1465 1470 Ser Gly Val Leu Trp Asp Val
Pro Ser Pro Pro Glu Thr Gln Lys 1475 1480
1485 Ala Glu Leu Glu Glu Gly Val Tyr Arg Ile Lys Gln
Gln Gly Ile 1490 1495 1500
Phe Gly Lys Thr Gln Val Gly Val Gly Val Gln Lys Glu Gly Val 1505
1510 1515 Phe His Thr Met Trp
His Val Thr Arg Gly Ala Val Leu Thr His 1520 1525
1530 Asn Gly Lys Arg Leu Glu Pro Asn Trp Ala
Ser Val Lys Lys Asp 1535 1540 1545
Leu Ile Ser Tyr Gly Gly Gly Trp Arg Leu Ser Ala Gln Trp Gln
1550 1555 1560 Lys Gly
Glu Glu Val Gln Val Ile Ala Val Glu Pro Gly Lys Asn 1565
1570 1575 Pro Lys Asn Phe Gln Thr Met
Pro Gly Ile Phe Gln Thr Thr Thr 1580 1585
1590 Gly Glu Ile Gly Ala Ile Ala Leu Asp Phe Lys Pro
Gly Thr Ser 1595 1600 1605
Gly Ser Pro Ile Ile Asn Arg Glu Gly Lys Val Val Gly Leu Tyr 1610
1615 1620 Gly Asn Gly Val Val
Thr Lys Asn Gly Gly Tyr Val Ser Gly Ile 1625 1630
1635 Ala Gln Thr Asn Ala Glu Pro Asp Gly Pro
Thr Pro Glu Leu Glu 1640 1645 1650
Glu Glu Met Phe Lys Lys Arg Asn Leu Thr Ile Met Asp Leu His
1655 1660 1665 Pro Gly
Ser Gly Lys Thr Arg Lys Tyr Leu Pro Ala Ile Val Arg 1670
1675 1680 Glu Ala Ile Lys Arg Arg Leu
Arg Thr Leu Ile Leu Ala Pro Thr 1685 1690
1695 Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu Lys
Gly Leu Pro 1700 1705 1710
Ile Arg Tyr Gln Thr Thr Ala Thr Lys Ser Glu His Thr Gly Arg 1715
1720 1725 Glu Ile Val Asp Leu
Met Cys His Ala Thr Phe Thr Met Arg Leu 1730 1735
1740 Leu Ser Pro Val Arg Val Pro Asn Tyr Asn
Leu Ile Ile Met Asp 1745 1750 1755
Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly Tyr
1760 1765 1770 Ile Ser
Thr Arg Val Gly Met Gly Glu Ala Ala Ala Ile Phe Met 1775
1780 1785 Thr Ala Thr Pro Pro Gly Thr
Ala Asp Ala Phe Pro Gln Ser Asn 1790 1795
1800 Ala Pro Ile Gln Asp Glu Glu Arg Asp Ile Pro Glu
Arg Ser Trp 1805 1810 1815
Asn Ser Gly Asn Glu Trp Ile Thr Asp Phe Val Gly Lys Thr Val 1820
1825 1830 Trp Phe Val Pro Ser
Ile Lys Ala Gly Asn Asp Ile Ala Asn Cys 1835 1840
1845 Leu Arg Lys Asn Gly Lys Lys Val Ile Gln
Leu Ser Arg Lys Thr 1850 1855 1860
Phe Asp Thr Glu Tyr Gln Lys Thr Lys Leu Asn Asp Trp Asp Phe
1865 1870 1875 Val Val
Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys Ala 1880
1885 1890 Asp Arg Val Ile Asp Pro Arg
Arg Cys Leu Lys Pro Val Ile Leu 1895 1900
1905 Thr Asp Gly Pro Glu Arg Val Ile Leu Ala Gly Pro
Met Pro Val 1910 1915 1920
Thr Val Ala Ser Ala Ala Gln Arg Arg Gly Arg Val Gly Arg Asn 1925
1930 1935 Pro Gln Lys Glu Asn
Asp Gln Tyr Ile Phe Met Gly Gln Pro Leu 1940 1945
1950 Asn Asn Asp Glu Asp His Ala His Trp Thr
Glu Ala Lys Met Leu 1955 1960 1965
Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ala Leu Phe
1970 1975 1980 Glu Pro
Glu Arg Glu Lys Ser Ala Ala Ile Asp Gly Glu Tyr Arg 1985
1990 1995 Leu Lys Gly Glu Ser Arg Lys
Thr Phe Val Glu Leu Met Arg Arg 2000 2005
2010 Gly Asp Leu Pro Val Trp Leu Ala His Lys Val Ala
Ser Glu Gly 2015 2020 2025
Ile Lys Tyr Thr Asp Arg Lys Trp Cys Phe Asp Gly Glu Arg Asn 2030
2035 2040 Asn Gln Ile Leu Glu
Glu Asn Met Asp Val Glu Ile Trp Thr Lys 2045 2050
2055 Glu Gly Glu Lys Lys Lys Leu Arg Pro Arg
Trp Leu Asp Ala Arg 2060 2065 2070
Thr Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Asp Phe Ala
2075 2080 2085 Ala Gly
Arg Lys Ser Ile Ala Leu Asp Leu Val Thr Glu Ile Gly 2090
2095 2100 Arg Val Pro Ser His Leu Ala
His Arg Thr Arg Asn Ala Leu Asp 2105 2110
2115 Asn Leu Val Met Leu His Thr Ser Glu His Gly Gly
Arg Ala Tyr 2120 2125 2130
Arg His Ala Val Glu Glu Leu Pro Glu Thr Met Glu Thr Leu Leu 2135
2140 2145 Leu Leu Gly Leu Met
Ile Leu Leu Thr Gly Gly Ala Met Leu Phe 2150 2155
2160 Leu Ile Ser Gly Lys Gly Ile Gly Lys Thr
Ser Ile Gly Leu Ile 2165 2170 2175
Cys Val Ile Ala Ser Ser Gly Met Leu Trp Met Ala Asp Val Pro
2180 2185 2190 Leu Gln
Trp Ile Ala Ser Ala Ile Val Leu Glu Phe Phe Met Met 2195
2200 2205 Val Leu Leu Ile Pro Glu Pro
Glu Lys Gln Arg Thr Pro Gln Asp 2210 2215
2220 Asn Gln Leu Ala Tyr Val Val Ile Gly Ile Leu Thr
Leu Ala Ala 2225 2230 2235
Ile Val Ala Ala Asn Glu Met Gly Leu Leu Glu Thr Thr Lys Arg 2240
2245 2250 Asp Leu Gly Met Ser
Lys Glu Pro Gly Val Val Ser Pro Thr Ser 2255 2260
2265 Tyr Leu Asp Val Asp Leu His Pro Ala Ser
Ala Trp Thr Leu Tyr 2270 2275 2280
Ala Val Ala Thr Thr Val Ile Thr Pro Met Leu Arg His Thr Ile
2285 2290 2295 Glu Asn
Ser Thr Ala Asn Val Ser Leu Ala Ala Ile Ala Asn Gln 2300
2305 2310 Ala Val Val Leu Met Gly Leu
Asp Lys Gly Trp Pro Ile Ser Lys 2315 2320
2325 Met Asp Leu Gly Val Pro Leu Leu Ala Leu Gly Cys
Tyr Ser Gln 2330 2335 2340
Val Asn Pro Leu Thr Leu Ala Ala Ala Val Leu Leu Leu Val Thr 2345
2350 2355 His Tyr Ala Ile Ile
Gly Pro Gly Leu Gln Ala Lys Ala Thr Arg 2360 2365
2370 Glu Ala Gln Lys Arg Thr Ala Ala Gly Ile
Met Lys Asn Pro Thr 2375 2380 2385
Val Asp Gly Ile Met Thr Ile Asp Leu Asp Pro Val Ile Tyr Asp
2390 2395 2400 Ser Lys
Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val Leu 2405
2410 2415 Cys Ala Val Gln Leu Leu Leu
Met Arg Thr Ser Trp Ala Leu Cys 2420 2425
2430 Glu Val Leu Thr Leu Ala Thr Gly Pro Ile Thr Thr
Leu Trp Glu 2435 2440 2445
Gly Ser Pro Gly Lys Phe Trp Asn Thr Thr Ile Ala Val Ser Met 2450
2455 2460 Ala Asn Ile Phe Arg
Gly Ser Tyr Leu Ala Gly Ala Gly Leu Ala 2465 2470
2475 Phe Ser Ile Met Lys Ser Val Gly Thr Gly
Lys Arg Gly Thr Gly 2480 2485 2490
Ser Gln Gly Glu Thr Leu Gly Glu Lys Trp Lys Lys Lys Leu Asn
2495 2500 2505 Gln Leu
Ser Arg Lys Glu Phe Asp Leu Tyr Lys Lys Ser Gly Ile 2510
2515 2520 Thr Glu Val Asp Arg Thr Glu
Ala Lys Glu Gly Leu Lys Arg Gly 2525 2530
2535 Glu Ile Thr His His Ala Val Ser Arg Gly Ser Ala
Lys Leu Gln 2540 2545 2550
Trp Phe Val Glu Arg Asn Met Val Ile Pro Glu Gly Arg Val Ile 2555
2560 2565 Asp Leu Gly Cys Gly
Arg Gly Gly Trp Ser Tyr Tyr Cys Ala Gly 2570 2575
2580 Leu Lys Lys Val Thr Glu Val Arg Gly Tyr
Thr Lys Gly Gly Pro 2585 2590 2595
Gly His Glu Glu Pro Val Pro Met Ser Thr Tyr Gly Trp Asn Ile
2600 2605 2610 Val Lys
Leu Met Ser Gly Lys Asp Val Phe Tyr Leu Pro Pro Glu 2615
2620 2625 Lys Cys Asp Thr Leu Leu Cys
Asp Ile Gly Glu Ser Ser Pro Ser 2630 2635
2640 Pro Thr Val Glu Glu Ser Arg Thr Ile Arg Val Leu
Lys Met Val 2645 2650 2655
Glu Pro Trp Leu Lys Asn Asn Gln Phe Cys Ile Lys Val Leu Asn 2660
2665 2670 Pro Tyr Met Pro Thr
Val Ile Glu His Leu Glu Arg Leu Gln Arg 2675 2680
2685 Lys His Gly Gly Met Leu Val Arg Asn Pro
Leu Ser Arg Asn Ser 2690 2695 2700
Thr His Glu Met Tyr Trp Ile Ser Asn Gly Thr Gly Asn Ile Val
2705 2710 2715 Ser Ser
Val Asn Met Val Ser Arg Leu Leu Leu Asn Arg Phe Thr 2720
2725 2730 Met Thr His Arg Arg Pro Thr
Ile Glu Lys Asp Val Asp Leu Gly 2735 2740
2745 Ala Gly Thr Arg His Val Asn Ala Glu Pro Glu Thr
Pro Asn Met 2750 2755 2760
Asp Val Ile Gly Glu Arg Ile Lys Arg Ile Lys Glu Glu His Ser 2765
2770 2775 Ser Thr Trp His Tyr
Asp Asp Glu Asn Pro Tyr Lys Thr Trp Ala 2780 2785
2790 Tyr His Gly Ser Tyr Glu Val Lys Ala Thr
Gly Ser Ala Ser Ser 2795 2800 2805
Met Ile Asn Gly Val Val Lys Leu Leu Thr Lys Pro Trp Asp Val
2810 2815 2820 Val Pro
Met Val Thr Gln Met Ala Met Thr Asp Thr Thr Pro Phe 2825
2830 2835 Gly Gln Gln Arg Val Phe Lys
Glu Lys Val Asp Thr Arg Thr Pro 2840 2845
2850 Arg Pro Met Pro Gly Thr Arg Lys Val Met Glu Ile
Thr Ala Glu 2855 2860 2865
Trp Leu Trp Arg Thr Leu Gly Arg Asn Lys Arg Pro Arg Leu Cys 2870
2875 2880 Thr Arg Glu Glu Phe
Thr Lys Lys Val Arg Thr Asn Ala Ala Met 2885 2890
2895 Gly Ala Val Phe Thr Glu Glu Asn Gln Trp
Asp Ser Ala Arg Ala 2900 2905 2910
Ala Val Glu Asp Glu Glu Phe Trp Lys Leu Val Asp Arg Glu Arg
2915 2920 2925 Glu Leu
His Lys Leu Gly Lys Cys Gly Ser Cys Val Tyr Asn Met 2930
2935 2940 Met Gly Lys Arg Glu Lys Lys
Leu Gly Glu Phe Gly Lys Ala Lys 2945 2950
2955 Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala
Arg Tyr Leu 2960 2965 2970
Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Phe Ser 2975
2980 2985 Arg Glu Asn Ser Tyr
Ser Gly Val Glu Gly Glu Gly Leu His Lys 2990 2995
3000 Leu Gly Tyr Ile Leu Arg Asp Ile Ser Lys
Ile Pro Gly Gly Ala 3005 3010 3015
Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Glu
3020 3025 3030 Asp Asp
Leu His Asn Glu Glu Lys Ile Thr Gln Gln Met Asp Pro 3035
3040 3045 Glu His Arg Gln Leu Ala Asn
Ala Ile Phe Lys Leu Thr Tyr Gln 3050 3055
3060 Asn Lys Val Val Lys Val Gln Arg Pro Thr Pro Lys
Gly Thr Val 3065 3070 3075
Met Asp Ile Ile Ser Arg Lys Asp Gln Arg Gly Ser Gly Gln Val 3080
3085 3090 Gly Thr Tyr Gly Leu
Asn Thr Phe Thr Asn Met Glu Ala Gln Leu 3095 3100
3105 Ile Arg Gln Met Glu Gly Glu Gly Val Leu
Ser Lys Ala Asp Leu 3110 3115 3120
Glu Asn Pro His Pro Leu Glu Lys Lys Ile Thr Gln Trp Leu Glu
3125 3130 3135 Thr Lys
Gly Val Glu Arg Leu Lys Arg Met Ala Ile Ser Gly Asp 3140
3145 3150 Asp Cys Val Val Lys Pro Ile
Asp Asp Arg Phe Ala Asn Ala Leu 3155 3160
3165 Leu Ala Leu Asn Asp Met Gly Lys Val Arg Lys Asp
Ile Pro Gln 3170 3175 3180
Trp Gln Pro Ser Lys Gly Trp His Asp Trp Gln Gln Val Pro Phe 3185
3190 3195 Cys Ser His His Phe
His Glu Leu Ile Met Lys Asp Gly Arg Lys 3200 3205
3210 Leu Val Val Pro Cys Arg Pro Gln Asp Glu
Leu Ile Gly Arg Ala 3215 3220 3225
Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala Cys
3230 3235 3240 Leu Gly
Lys Ala Tyr Ala Gln Met Trp Ala Leu Met Tyr Phe His 3245
3250 3255 Arg Arg Asp Leu Arg Leu Ala
Ser Asn Ala Ile Cys Ser Ala Val 3260 3265
3270 Pro Val His Trp Val Pro Thr Ser Arg Thr Thr Trp
Ser Ile His 3275 3280 3285
Ala His His Gln Trp Met Thr Thr Glu Asp Met Leu Thr Val Trp 3290
3295 3300 Asn Arg Val Trp Ile
Glu Asp Asn Pro Trp Met Glu Asp Lys Thr 3305 3310
3315 Pro Val Thr Thr Trp Glu Asp Val Pro Tyr
Leu Gly Lys Arg Glu 3320 3325 3330
Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala Thr
3335 3340 3345 Trp Ala
Gln Asn Ile Leu Thr Ala Ile Gln Gln Val Arg Ser Leu 3350
3355 3360 Ile Gly Asn Glu Glu Phe Leu
Asp Tyr Met Pro Ser Met Lys Arg 3365 3370
3375 Phe Arg Lys Glu Glu Glu Ser Glu Gly Ala Ile Trp
3380 3385 3390
125PRTArtificialSynthetic construct 12Gly Ala Gly Lys Thr 1
5 135PRTArtificialSynthetic construct 13Gly Arg Ile Gly Arg 1
5 1410723DNAArtificial SequenceDerived from Dengue virus serotype
2/Dengue virus serotype 1, MVS 14agttgttagt ctacgtggac cgacaaagac
agattctttg agggagctaa gctcaatgta 60gttctaacag ttttttaatt agagagcaga
tctctgatga ataaccaacg gaaaaaggcg 120aaaaacacgc ctttcaatat gctgaaacgc
gagagaaacc gcgtgtcgac tgtgcaacag 180ctgacaaaga gattctcact tggaatgctg
cagggacgag gaccattaaa actgttcatg 240gccctggtgg cgttccttcg tttcctaaca
atcccaccaa cagcagggat attgaagaga 300tggggaacaa ttaaaaaatc aaaagctatt
aatgttttga gagggttcag gaaagagatt 360ggaaggatgc tgaacatctt gaataggaga
cgcagatctg caggcatgat cattatgctg 420attccaacag tgatggcgtt ccatttaacc
acgcgtgggg gagagccgca tatgatagtt 480agcaagcagg aaagaggaaa gtcacttttg
ttcaagacct ctgcaggtgt caacatgtgc 540accctcattg cgatggattt gggagagttg
tgtgaggaca cgatgaccta caaatgcccc 600cggatcactg aggcggaacc agatgacgtt
gactgttggt gcaatgccac ggacacatgg 660gtgacctatg gaacgtgctc tcaaactggc
gaacaccgac gagacaaacg ttccgtcgca 720ttggccccac acgtggggct tggcctagaa
acaagagccg aaacgtggat gtcctctgaa 780ggtgcttgga aacagataca aaaagtagag
acttgggctc tgagacatcc aggattcacg 840gtgatagccc tttttctagc acatgccata
ggaacatcca tcacccagaa agggatcatt 900ttcattttgc tgatgctggt aacaccatct
atggccatgc gatgcgtggg aataggcaac 960agagacttcg tggaaggact gtcaggagca
acatgggtgg atgtggtact ggagcatgga 1020agttgcgtca ccaccatggc aaaaaacaaa
ccaacactgg acattgaact cttgaagacg 1080gaggtcacaa accctgcagt tctgcgtaaa
ttgtgcattg aagctaaaat atcaaacacc 1140accaccgatt cgagatgtcc aacacaagga
gaagccacac tggtggaaga acaagacgcg 1200aactttgtgt gccgacgaac gttcgtggac
agaggctggg gcaatggctg tgggctattc 1260ggaaaaggta gtctaataac gtgtgccaag
tttaagtgtg tgacaaaact agaaggaaag 1320atagttcaat atgaaaacct aaaatattca
gtgatagtca ccgtccacac tggagatcag 1380caccaggtgg gaaatgagac tacagaacat
ggaacaactg caaccataac acctcaagct 1440cctacgtcgg aaatacagct gaccgactac
ggaaccctta cattagattg ttcacctagg 1500acagggctag attttaacga gatggtgttg
ctgacaatga aagaaagatc atggcttgtc 1560cacaaacaat ggttcctaga cttaccactg
ccttggacct ctggggcttc aacatcccaa 1620gagacttgga acagacaaga tttactggtc
acatttaaga cagctcatgc aaagaagcag 1680gaagtagtcg tactaggatc acaagaagga
gcaatgcaca ctgcgctgac tggagcgaca 1740gaaatccaaa cgtcaggaac gacaacaatt
ttcgcaggac acctaaaatg cagactaaaa 1800atggacaaac taactttaaa agggatgtca
tatgtgatgt gcacaggctc attcaagtta 1860gagaaagaag tggctgagac ccagcatgga
actgttctgg tgcaggttaa atatgaagga 1920acagacgcac catgcaagat tcccttttcg
acccaagatg agaaaggagc aacccagaat 1980gggagattaa taacagccaa ccccatagtc
actgacaaag aaaaaccagt caatattgag 2040gcagaaccac cctttggtga gagctacatc
gtggtaggag caggtgaaaa agctttgaaa 2100ctaagctggt tcaagaaagg aagcagcata
gggaaaatgt ttgaagcaac tgcccgagga 2160gcacgaagga tggccattct gggagacacc
gcatgggact tcggttctat aggaggagtg 2220ttcacgtcta tgggaaaact ggtacaccag
gtttttggaa ctgcatatgg agttttgttt 2280agcggagttt cttggaccat gaaaatagga
atagggattc tgctgacatg gctaggatta 2340aattcaagga acacgtccct ttcgatgatg
tgcatcgcag ccggcattgt gacactgtat 2400ttgggagtca tggtgcaggc cgatagtggt
tgcgttgtga gctggaaaaa caaagaactg 2460aaatgtggca gtgggatttt catcacagac
aacgtgcaca catggacaga acaatacaag 2520ttccaaccag aatccccttc aaaactagct
tcagctatcc agaaagccca tgaagaggac 2580atttgtggaa tccgctcagt aacaagactg
gagaatctga tgtggaaaca aataacacca 2640gaattgaatc acattctatc agaaaatgag
gtgaagttaa ctattatgac aggagacatc 2700aaaggaatca tgcaggcagg aaaacgatct
ctgcggcctc agcccactga gctgaagtat 2760tcatggaaaa catggggcaa agcaaaaatg
ctctctacag agtctcataa ccagaccttt 2820ctcattgatg gccccgaaac agcagaatgc
cccaacacaa atagagcttg gaattcgttg 2880gaagttgaag actatggctt tggagtattc
accaccaata tatggctaaa attgaaagaa 2940aaacaggatg tattctgcga ctcaaaactc
atgtcagcgg ccataaaaga caacagagcc 3000gtccatgccg atatgggtta ttggatagaa
agtgcactca atgacacatg gaagatagag 3060aaagcctctt tcattgaagt taaaaactgc
cactggccaa aatcacacac cctctggagc 3120aatggagtgc tagaaagtga gatgataatt
ccaaagaatc tcgctggacc agtgtctcaa 3180cacaactata gaccaggcta ccatacacaa
ataacaggac catggcatct aggtaagctt 3240gagatggact ttgatttctg tgatggaaca
acagtggtag tgactgagga ctgcggaaat 3300agaggaccct ctttgagaac aaccactgcc
tctggaaaac tcataacaga atggtgctgc 3360cgatcttgca cattaccacc gctaagatac
agaggtgagg atgggtgctg gtacgggatg 3420gaaatcagac cattgaagga gaaagaagag
aatttggtca actccttggt cacagctgga 3480catgggcagg tcgacaactt ttcactagga
gtcttgggaa tggcattgtt cctggaggaa 3540atgcttagga cccgagtagg aacgaaacat
gcaatactac tagttgcagt ttcttttgtg 3600acattgatca cagggaacat gtcctttaga
gacctgggaa gagtgatggt tatggtaggc 3660gccactatga cggatgacat aggtatgggc
gtgacttatc ttgccctact agcagccttc 3720aaagtcagac caacttttgc agctggacta
ctcttgagaa agctgacctc caaggaattg 3780atgatgacta ctataggaat tgtactcctc
tcccagagca ccctaccaga gaccattctt 3840gagttgactg atgcgttagc cttaggcatg
atggtcctca aaatggtgag aaatatggaa 3900aagtatcaat tggcagtgac tatcatggct
atcttgtgcg tcccaaacgc agtgatatta 3960caaaacgcat ggaaagtgag ttgcacaata
ttggcagtgg tgtccgtttc cccactgttc 4020ttaacatcct cacagcaaaa aacagattgg
ataccattag cattgacgat caaaggtctc 4080aatccaacag ctatttttct aacaaccctc
tcaagaacca gcaagaaaag gagctggcca 4140ttaaatgagg ctatcatggc agtcgggatg
gtgagcattt tagccagttc tctcctaaaa 4200aatgatattc ccatgacagg accattagtg
gctggagggc tcctcactgt gtgctacgtg 4260ctcactggac gatcggccga tttggaactg
gagagagcag ccgatgtcaa atgggaagac 4320caggcagaga tatcaggaag cagtccaatc
ctgtcaataa caatatcaga agatggtagc 4380atgtcgataa aaaatgaaga ggaagatcaa
acactgacca tactcattag aacaggattg 4440ctggtgatct caggactttt tcctgtatca
ataccaatca cggcagcagc atggtacctg 4500tgggaagtga agaaacaacg ggccggagta
ttgtgggatg ttccttcacc cccacccatg 4560ggaaaggctg aactggaaga tggagcctat
agaattaagc aaaaagggat tcttggatat 4620tcccagatcg gagccggagt ttacaaagaa
ggaacattcc atacaatgtg gcatgtcaca 4680cgtggcgctg ttctaatgca taaaggaaag
aggattgaac catcatgggc ggacgtcaag 4740aaagacctaa tatcatatgg aggaggctgg
aagttagaag gagaatggaa ggaaggagaa 4800gaagtccagg tattggcact ggagcctgga
aaaaatccaa gagccgtcca aacgaaacct 4860ggtcttttca aaaccaacgc cggaacaata
ggtgctgtat ctctggactt ttctcctgga 4920acgtcaggat ctccaattat cgacaaaaaa
ggaaaagttg tgggtcttta tggtaatggt 4980gttgttacaa ggagtggagc atatgtgagt
gctatagccc agactgaaaa aagcattgaa 5040gacaacccag agatcgaaga tgacattttc
cgaaagagaa gactgaccat catggacctc 5100cacccaggag cgggaaagac gaagagatac
cttccggcca tagtcagaga agctataaaa 5160cggggtttga gaacattaat cttggccccc
actagagttg tggcagctga aatggaggaa 5220gcccttagag gacttccaat aagataccag
accccagcca tcagagctgt gcacaccggg 5280cgggagattg tggacctaat gtgtcatgcc
acatttacca tgaggctgct atcaccagtt 5340agagtgccaa actacaacct gattatcatg
gacgaagccc atttcacaga cccagcaagt 5400atagcagcta gaggatacat ctcaactcga
gtggagatgg gtgaggcagc tgggattttt 5460atgacagcca ctcccccggg aagcagagac
ccatttcctc agagcaatgc accaatcata 5520gatgaagaaa gagaaatccc tgaacgctcg
tggaattccg gacatgaatg ggtcacggat 5580tttaaaggga agactgtttg gttcgttcca
agtataaaag caggaaatga tatagcagct 5640tgcctgagga aaaatggaaa gaaagtgata
caactcagta ggaagacctt tgattctgag 5700tatgtcaaga ctagaaccaa tgattgggac
ttcgtggtta caactgacat ttcagaaatg 5760ggtgccaatt tcaaggctga gagggttata
gaccccagac gctgcatgaa accagtcata 5820ctaacagatg gtgaagagcg ggtgattctg
gcaggaccta tgccagtgac ccactctagt 5880gcagcacaaa gaagagggag aataggaaga
aatccaaaaa atgagaatga ccagtacata 5940tacatggggg aacctctgga aaatgatgaa
gactgtgcac actggaaaga agctaaaatg 6000ctcctagata acatcaacac gccagaagga
atcattccta gcatgttcga accagagcgt 6060gaaaaggtgg atgccattga tggcgaatac
cgcttgagag gagaagcaag gaaaaccttt 6120gtagacttaa tgagaagagg agacctacca
gtctggttgg cctacagagt ggcagctgaa 6180ggcatcaact acgcagacag aaggtggtgt
tttgatggag tcaagaacaa ccaaatccta 6240gaagaaaacg tggaagttga aatctggaca
aaagaagggg aaaggaagaa attgaaaccc 6300agatggttgg atgctaggat ctattctgac
ccactggcgc taaaagaatt taaggaattt 6360gcagccggaa gaaagtctct gaccctgaac
ctaatcacag aaatgggtag gctcccaacc 6420ttcatgactc agaaggcaag agacgcactg
gacaacttag cagtgctgca cacggctgag 6480gcaggtggaa gggcgtacaa ccatgctctc
agtgaactgc cggagaccct ggagacattg 6540cttttactga cacttctggc tacagtcacg
ggagggatct ttttattctt gatgagcgca 6600aggggcatag ggaagatgac cctgggaatg
tgctgcataa tcacggctag catcctccta 6660tggtacgcac aaatacagcc acactggata
gcagcttcaa taatactgga gttttttctc 6720atagttttgc ttattccaga acctgaaaaa
cagagaacac cccaagacaa ccaactgacc 6780tacgttgtca tagccatcct cacagtggtg
gccgcaacca tggcaaacga gatgggtttc 6840ctagaaaaaa cgaagaaaga tctcggattg
ggaagcattg caacccagca acccgagagc 6900aacatcctgg acatagatct acgtcctgca
tcagcatgga cgctgtatgc cgtggccaca 6960acatttgtta caccaatgtt gagacatagc
attgaaaatt cctcagtgaa tgtgtcccta 7020acagctatag ccaaccaagc cacagtgtta
atgggtctcg ggaaaggatg gccattgtca 7080aagatggaca tcggagttcc ccttctcgcc
attggatgct actcacaagt caaccccata 7140actctcacag cagctctttt cttattggta
gcacattatg ccatcatagg gccaggactc 7200caagcaaaag caaccagaga agctcagaaa
agagcagcgg cgggcatcat gaaaaaccca 7260actgtcgatg gaataacagt gattgaccta
gatccaatac cttatgatcc gaagtttgaa 7320aagcagttgg gacaagtaat gctcctagtc
ctctgcgtga ctcaagtatt gatgatgagg 7380actacatggg ctctgtgtga ggctttaacc
ttagctaccg ggcccatctc cacattgtgg 7440gaaggaaatc cagggaggtt ttggaacact
accattgcgg tgtcaatggc taacattttt 7500agagggagtt acttggccgg agctggactt
ctcttttcta ttatgaagaa cacaaccaac 7560acaagaaggg gaactggcaa cataggagag
acgcttggag agaaatggaa aagccgattg 7620aacgcattgg gaaaaagtga attccagatc
tacaagaaaa gtggaatcca ggaagtggat 7680agaaccttag caaaagaagg cattaaaaga
ggagaaacgg accatcacgc tgtgtcgcga 7740ggctcagcaa aactgagatg gttcgttgag
agaaacatgg tcacaccaga agggaaagta 7800gtggacctcg gttgtggcag aggaggctgg
tcatactatt gtggaggact aaagaatgta 7860agagaagtca aaggcctaac aaaaggagga
ccaggacacg aagaacccat ccccatgtca 7920acatatgggt ggaatctagt gcgtcttcaa
agtggagttg acgttttctt catcccgcca 7980gaaaagtgtg acacattatt gtgtgacata
ggggagtcat caccaaatcc cacagtggaa 8040gcaggacgaa cactcagagt ccttaactta
gtagaaaatt ggttgaacaa caacactcaa 8100ttttgcataa aggttctcaa cccatatatg
ccctcagtca tagaaaaaat ggaagcacta 8160caaaggaaat atggaggagc cttagtgagg
aatccactct cacgaaactc cacacatgag 8220atgtactggg tatccaatgc ttccgggaac
atagtgtcat cagtgaacat gatttcaagg 8280atgttgatca acagatttac aatgagatac
aagaaagcca cttacgagcc ggatgttgac 8340ctcggaagcg gaacccgtaa catcgggatt
gaaagtgaga taccaaacct agatataatt 8400gggaaaagaa tagaaaaaat aaagcaagag
catgaaacat catggcacta tgaccaagac 8460cacccataca aaacgtgggc ataccatggt
agctatgaaa caaaacagac tggatcagca 8520tcatccatgg tcaacggagt ggtcaggctg
ctgacaaaac cttgggacgt cgtccccatg 8580gtgacacaga tggcaatgac agacacgact
ccatttggac aacagcgcgt ttttaaagag 8640aaagtggaca cgagaaccca agaaccgaaa
gaaggcacga agaaactaat gaaaataaca 8700gcagagtggc tttggaaaga attagggaag
aaaaagacac ccaggatgtg caccagagaa 8760gaattcacaa gaaaggtgag aagcaatgca
gccttggggg ccatattcac tgatgagaac 8820aagtggaagt cggcacgtga ggctgttgaa
gatagtaggt tttgggagct ggttgacaag 8880gaaaggaatc tccatcttga aggaaagtgt
gaaacatgtg tgtacaacat gatgggaaaa 8940agagagaaga agctagggga attcggcaag
gcaaaaggca gcagagccat atggtacatg 9000tggcttggag cacgcttctt agagtttgaa
gccctaggat tcttaaatga agatcactgg 9060ttctccagag agaactccct gagtggagtg
gaaggagaag ggctgcacaa gctaggttac 9120attctaagag acgtgagcaa gaaagaggga
ggagcaatgt atgccgatga caccgcagga 9180tgggatacaa gaatcacact agaagaccta
aaaaatgaag aaatggtaac aaaccacatg 9240gaaggagaac acaagaaact agccgaggcc
attttcaaac taacgtacca aaacaaggtg 9300gtgcgtgtgc aaagaccaac accaagaggc
acagtaatgg acatcatatc gagaagagac 9360caaagaggta gtggacaagt tggcacctat
ggactcaata ctttcaccaa tatggaagcc 9420caactaatca gacagatgga gggagaagga
gtctttaaaa gcattcagca cctaacaatc 9480acagaagaaa tcgctgtgca aaactggtta
gcaagagtgg ggcgcgaaag gttatcaaga 9540atggccatca gtggagatga ttgtgttgtg
aaacctttag atgacaggtt cgcaagcgct 9600ttaacagctc taaatgacat gggaaagatt
aggaaagaca tacaacaatg ggaaccttca 9660agaggatgga atgattggac acaagtgccc
ttctgttcac accatttcca tgagttaatc 9720atgaaagacg gtcgcgtact cgttgttcca
tgtagaaacc aagatgaact gattggcaga 9780gcccgaatct cccaaggagc agggtggtct
ttgcgggaga cggcctgttt ggggaagtct 9840tacgcccaaa tgtggagctt gatgtacttc
cacagacgcg acctcaggct ggcggcaaat 9900gctatttgct cggcagtacc atcacattgg
gttccaacaa gtcgaacaac ctggtccata 9960catgctaaac atgaatggat gacaacggaa
gacatgctga cagtctggaa cagggtgtgg 10020attcaagaaa acccatggat ggaagacaaa
actccagtgg aatcatggga ggaaatccca 10080tacttgggga aaagagaaga ccaatggtgc
ggctcattga ttgggttaac aagcagggcc 10140acctgggcaa agaacatcca agcagcaata
aatcaagtta gatcccttat aggcaatgaa 10200gaatacacag attacatgcc atccatgaaa
agattcagaa gagaagagga agaagcagga 10260gttctgtggt agaaagcaaa actaacatga
aacaaggcta gaagtcaggt cggattaagc 10320catagtacgg aaaaaactat gctacctgtg
agccccgtcc aaggacgtta aaagaagtca 10380ggccatcata aatgccatag cttgagtaaa
ctatgcagcc tgtagctcca cctgagaagg 10440tgtaaaaaat ccgggaggcc acaaaccatg
gaagctgtac gcatggcgta gtggactagc 10500ggttagagga gacccctccc ttacaaatcg
cagcaacaat gggggcccaa ggcgagatga 10560agctgtagtc tcgctggaag gactagaggt
tagaggagac ccccccgaaa caaaaaacag 10620catattgacg ctgggaaaga ccagagatcc
tgctgtctcc tcagcatcat tccaggcaca 10680gaacgccaga aaatggaatg gtgctgttga
atcaacaggt tct 10723153391PRTArtificial
SequencePolypeptide, Derived from Dengue virus serotype 2/Dengue
virus serotype 1, MVS 15Met Asn Asn Gln Arg Lys Lys Ala Lys Asn Thr Pro
Phe Asn Met Leu 1 5 10
15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu Thr Lys Arg
20 25 30 Phe Ser Leu
Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met 35
40 45 Ala Leu Val Ala Phe Leu Arg Phe
Leu Thr Ile Pro Pro Thr Ala Gly 50 55
60 Ile Leu Lys Arg Trp Gly Thr Ile Lys Lys Ser Lys Ala
Ile Asn Val 65 70 75
80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu Asn Ile Leu Asn
85 90 95 Arg Arg Arg Arg
Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val 100
105 110 Met Ala Phe His Leu Thr Thr Arg Gly
Gly Glu Pro His Met Ile Val 115 120
125 Ser Lys Gln Glu Arg Gly Lys Ser Leu Leu Phe Lys Thr Ser
Ala Gly 130 135 140
Val Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Leu Cys Glu 145
150 155 160 Asp Thr Met Thr Tyr
Lys Cys Pro Arg Ile Thr Glu Ala Glu Pro Asp 165
170 175 Asp Val Asp Cys Trp Cys Asn Ala Thr Asp
Thr Trp Val Thr Tyr Gly 180 185
190 Thr Cys Ser Gln Thr Gly Glu His Arg Arg Asp Lys Arg Ser Val
Ala 195 200 205 Leu
Ala Pro His Val Gly Leu Gly Leu Glu Thr Arg Ala Glu Thr Trp 210
215 220 Met Ser Ser Glu Gly Ala
Trp Lys Gln Ile Gln Lys Val Glu Thr Trp 225 230
235 240 Ala Leu Arg His Pro Gly Phe Thr Val Ile Ala
Leu Phe Leu Ala His 245 250
255 Ala Ile Gly Thr Ser Ile Thr Gln Lys Gly Ile Ile Phe Ile Leu Leu
260 265 270 Met Leu
Val Thr Pro Ser Met Ala Met Arg Cys Val Gly Ile Gly Asn 275
280 285 Arg Asp Phe Val Glu Gly Leu
Ser Gly Ala Thr Trp Val Asp Val Val 290 295
300 Leu Glu His Gly Ser Cys Val Thr Thr Met Ala Lys
Asn Lys Pro Thr 305 310 315
320 Leu Asp Ile Glu Leu Leu Lys Thr Glu Val Thr Asn Pro Ala Val Leu
325 330 335 Arg Lys Leu
Cys Ile Glu Ala Lys Ile Ser Asn Thr Thr Thr Asp Ser 340
345 350 Arg Cys Pro Thr Gln Gly Glu Ala
Thr Leu Val Glu Glu Gln Asp Ala 355 360
365 Asn Phe Val Cys Arg Arg Thr Phe Val Asp Arg Gly Trp
Gly Asn Gly 370 375 380
Cys Gly Leu Phe Gly Lys Gly Ser Leu Ile Thr Cys Ala Lys Phe Lys 385
390 395 400 Cys Val Thr Lys
Leu Glu Gly Lys Ile Val Gln Tyr Glu Asn Leu Lys 405
410 415 Tyr Ser Val Ile Val Thr Val His Thr
Gly Asp Gln His Gln Val Gly 420 425
430 Asn Glu Thr Thr Glu His Gly Thr Thr Ala Thr Ile Thr Pro
Gln Ala 435 440 445
Pro Thr Ser Glu Ile Gln Leu Thr Asp Tyr Gly Thr Leu Thr Leu Asp 450
455 460 Cys Ser Pro Arg Thr
Gly Leu Asp Phe Asn Glu Met Val Leu Leu Thr 465 470
475 480 Met Lys Glu Arg Ser Trp Leu Val His Lys
Gln Trp Phe Leu Asp Leu 485 490
495 Pro Leu Pro Trp Thr Ser Gly Ala Ser Thr Ser Gln Glu Thr Trp
Asn 500 505 510 Arg
Gln Asp Leu Leu Val Thr Phe Lys Thr Ala His Ala Lys Lys Gln 515
520 525 Glu Val Val Val Leu Gly
Ser Gln Glu Gly Ala Met His Thr Ala Leu 530 535
540 Thr Gly Ala Thr Glu Ile Gln Thr Ser Gly Thr
Thr Thr Ile Phe Ala 545 550 555
560 Gly His Leu Lys Cys Arg Leu Lys Met Asp Lys Leu Thr Leu Lys Gly
565 570 575 Met Ser
Tyr Val Met Cys Thr Gly Ser Phe Lys Leu Glu Lys Glu Val 580
585 590 Ala Glu Thr Gln His Gly Thr
Val Leu Val Gln Val Lys Tyr Glu Gly 595 600
605 Thr Asp Ala Pro Cys Lys Ile Pro Phe Ser Thr Gln
Asp Glu Lys Gly 610 615 620
Ala Thr Gln Asn Gly Arg Leu Ile Thr Ala Asn Pro Ile Val Thr Asp 625
630 635 640 Lys Glu Lys
Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu Ser 645
650 655 Tyr Ile Val Val Gly Ala Gly Glu
Lys Ala Leu Lys Leu Ser Trp Phe 660 665
670 Lys Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ala Thr
Ala Arg Gly 675 680 685
Ala Arg Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe Gly Ser 690
695 700 Ile Gly Gly Val
Phe Thr Ser Met Gly Lys Leu Val His Gln Val Phe 705 710
715 720 Gly Thr Ala Tyr Gly Val Leu Phe Ser
Gly Val Ser Trp Thr Met Lys 725 730
735 Ile Gly Ile Gly Ile Leu Leu Thr Trp Leu Gly Leu Asn Ser
Arg Asn 740 745 750
Thr Ser Leu Ser Met Met Cys Ile Ala Ala Gly Ile Val Thr Leu Tyr
755 760 765 Leu Gly Val Met
Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys 770
775 780 Asn Lys Glu Leu Lys Cys Gly Ser
Gly Ile Phe Ile Thr Asp Asn Val 785 790
795 800 His Thr Trp Thr Glu Gln Tyr Lys Phe Gln Pro Glu
Ser Pro Ser Lys 805 810
815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu Glu Asp Ile Cys Gly Ile
820 825 830 Arg Ser Val
Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro 835
840 845 Glu Leu Asn His Ile Leu Ser Glu
Asn Glu Val Lys Leu Thr Ile Met 850 855
860 Thr Gly Asp Ile Lys Gly Ile Met Gln Ala Gly Lys Arg
Ser Leu Arg 865 870 875
880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala
885 890 895 Lys Met Leu Ser
Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly 900
905 910 Pro Glu Thr Ala Glu Cys Pro Asn Thr
Asn Arg Ala Trp Asn Ser Leu 915 920
925 Glu Val Glu Asp Tyr Gly Phe Gly Val Phe Thr Thr Asn Ile
Trp Leu 930 935 940
Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys Leu Met Ser 945
950 955 960 Ala Ala Ile Lys Asp
Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp 965
970 975 Ile Glu Ser Ala Leu Asn Asp Thr Trp Lys
Ile Glu Lys Ala Ser Phe 980 985
990 Ile Glu Val Lys Asn Cys His Trp Pro Lys Ser His Thr Leu
Trp Ser 995 1000 1005
Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro Lys Asn Leu Ala 1010
1015 1020 Gly Pro Val Ser Gln
His Asn Tyr Arg Pro Gly Tyr His Thr Gln 1025 1030
1035 Ile Thr Gly Pro Trp His Leu Gly Lys Leu
Glu Met Asp Phe Asp 1040 1045 1050
Phe Cys Asp Gly Thr Thr Val Val Val Thr Glu Asp Cys Gly Asn
1055 1060 1065 Arg Gly
Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile 1070
1075 1080 Thr Glu Trp Cys Cys Arg Ser
Cys Thr Leu Pro Pro Leu Arg Tyr 1085 1090
1095 Arg Gly Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile
Arg Pro Leu 1100 1105 1110
Lys Glu Lys Glu Glu Asn Leu Val Asn Ser Leu Val Thr Ala Gly 1115
1120 1125 His Gly Gln Val Asp
Asn Phe Ser Leu Gly Val Leu Gly Met Ala 1130 1135
1140 Leu Phe Leu Glu Glu Met Leu Arg Thr Arg
Val Gly Thr Lys His 1145 1150 1155
Ala Ile Leu Leu Val Ala Val Ser Phe Val Thr Leu Ile Thr Gly
1160 1165 1170 Asn Met
Ser Phe Arg Asp Leu Gly Arg Val Met Val Met Val Gly 1175
1180 1185 Ala Thr Met Thr Asp Asp Ile
Gly Met Gly Val Thr Tyr Leu Ala 1190 1195
1200 Leu Leu Ala Ala Phe Lys Val Arg Pro Thr Phe Ala
Ala Gly Leu 1205 1210 1215
Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu Met Met Thr Thr Ile 1220
1225 1230 Gly Ile Val Leu Leu
Ser Gln Ser Thr Leu Pro Glu Thr Ile Leu 1235 1240
1245 Glu Leu Thr Asp Ala Leu Ala Leu Gly Met
Met Val Leu Lys Met 1250 1255 1260
Val Arg Asn Met Glu Lys Tyr Gln Leu Ala Val Thr Ile Met Ala
1265 1270 1275 Ile Leu
Cys Val Pro Asn Ala Val Ile Leu Gln Asn Ala Trp Lys 1280
1285 1290 Val Ser Cys Thr Ile Leu Ala
Val Val Ser Val Ser Pro Leu Phe 1295 1300
1305 Leu Thr Ser Ser Gln Gln Lys Thr Asp Trp Ile Pro
Leu Ala Leu 1310 1315 1320
Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile Phe Leu Thr Thr Leu 1325
1330 1335 Ser Arg Thr Ser Lys
Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile 1340 1345
1350 Met Ala Val Gly Met Val Ser Ile Leu Ala
Ser Ser Leu Leu Lys 1355 1360 1365
Asn Asp Ile Pro Met Thr Gly Pro Leu Val Ala Gly Gly Leu Leu
1370 1375 1380 Thr Val
Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp Leu Glu Leu 1385
1390 1395 Glu Arg Ala Ala Asp Val Lys
Trp Glu Asp Gln Ala Glu Ile Ser 1400 1405
1410 Gly Ser Ser Pro Ile Leu Ser Ile Thr Ile Ser Glu
Asp Gly Ser 1415 1420 1425
Met Ser Ile Lys Asn Glu Glu Glu Asp Gln Thr Leu Thr Ile Leu 1430
1435 1440 Ile Arg Thr Gly Leu
Leu Val Ile Ser Gly Leu Phe Pro Val Ser 1445 1450
1455 Ile Pro Ile Thr Ala Ala Ala Trp Tyr Leu
Trp Glu Val Lys Lys 1460 1465 1470
Gln Arg Ala Gly Val Leu Trp Asp Val Pro Ser Pro Pro Pro Met
1475 1480 1485 Gly Lys
Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile Lys Gln Lys 1490
1495 1500 Gly Ile Leu Gly Tyr Ser Gln
Ile Gly Ala Gly Val Tyr Lys Glu 1505 1510
1515 Gly Thr Phe His Thr Met Trp His Val Thr Arg Gly
Ala Val Leu 1520 1525 1530
Met His Lys Gly Lys Arg Ile Glu Pro Ser Trp Ala Asp Val Lys 1535
1540 1545 Lys Asp Leu Ile Ser
Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu 1550 1555
1560 Trp Lys Glu Gly Glu Glu Val Gln Val Leu
Ala Leu Glu Pro Gly 1565 1570 1575
Lys Asn Pro Arg Ala Val Gln Thr Lys Pro Gly Leu Phe Lys Thr
1580 1585 1590 Asn Ala
Gly Thr Ile Gly Ala Val Ser Leu Asp Phe Ser Pro Gly 1595
1600 1605 Thr Ser Gly Ser Pro Ile Ile
Asp Lys Lys Gly Lys Val Val Gly 1610 1615
1620 Leu Tyr Gly Asn Gly Val Val Thr Arg Ser Gly Ala
Tyr Val Ser 1625 1630 1635
Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu Asp Asn Pro Glu Ile 1640
1645 1650 Glu Asp Asp Ile Phe
Arg Lys Arg Arg Leu Thr Ile Met Asp Leu 1655 1660
1665 His Pro Gly Ala Gly Lys Thr Lys Arg Tyr
Leu Pro Ala Ile Val 1670 1675 1680
Arg Glu Ala Ile Lys Arg Gly Leu Arg Thr Leu Ile Leu Ala Pro
1685 1690 1695 Thr Arg
Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly Leu 1700
1705 1710 Pro Ile Arg Tyr Gln Thr Pro
Ala Ile Arg Ala Val His Thr Gly 1715 1720
1725 Arg Glu Ile Val Asp Leu Met Cys His Ala Thr Phe
Thr Met Arg 1730 1735 1740
Leu Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Leu Ile Ile Met 1745
1750 1755 Asp Glu Ala His Phe
Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly 1760 1765
1770 Tyr Ile Ser Thr Arg Val Glu Met Gly Glu
Ala Ala Gly Ile Phe 1775 1780 1785
Met Thr Ala Thr Pro Pro Gly Ser Arg Asp Pro Phe Pro Gln Ser
1790 1795 1800 Asn Ala
Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro Glu Arg Ser 1805
1810 1815 Trp Asn Ser Gly His Glu Trp
Val Thr Asp Phe Lys Gly Lys Thr 1820 1825
1830 Val Trp Phe Val Pro Ser Ile Lys Ala Gly Asn Asp
Ile Ala Ala 1835 1840 1845
Cys Leu Arg Lys Asn Gly Lys Lys Val Ile Gln Leu Ser Arg Lys 1850
1855 1860 Thr Phe Asp Ser Glu
Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp 1865 1870
1875 Phe Val Val Thr Thr Asp Ile Ser Glu Met
Gly Ala Asn Phe Lys 1880 1885 1890
Ala Glu Arg Val Ile Asp Pro Arg Arg Cys Met Lys Pro Val Ile
1895 1900 1905 Leu Thr
Asp Gly Glu Glu Arg Val Ile Leu Ala Gly Pro Met Pro 1910
1915 1920 Val Thr His Ser Ser Ala Ala
Gln Arg Arg Gly Arg Ile Gly Arg 1925 1930
1935 Asn Pro Lys Asn Glu Asn Asp Gln Tyr Ile Tyr Met
Gly Glu Pro 1940 1945 1950
Leu Glu Asn Asp Glu Asp Cys Ala His Trp Lys Glu Ala Lys Met 1955
1960 1965 Leu Leu Asp Asn Ile
Asn Thr Pro Glu Gly Ile Ile Pro Ser Met 1970 1975
1980 Phe Glu Pro Glu Arg Glu Lys Val Asp Ala
Ile Asp Gly Glu Tyr 1985 1990 1995
Arg Leu Arg Gly Glu Ala Arg Lys Thr Phe Val Asp Leu Met Arg
2000 2005 2010 Arg Gly
Asp Leu Pro Val Trp Leu Ala Tyr Arg Val Ala Ala Glu 2015
2020 2025 Gly Ile Asn Tyr Ala Asp Arg
Arg Trp Cys Phe Asp Gly Val Lys 2030 2035
2040 Asn Asn Gln Ile Leu Glu Glu Asn Val Glu Val Glu
Ile Trp Thr 2045 2050 2055
Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro Arg Trp Leu Asp Ala 2060
2065 2070 Arg Ile Tyr Ser Asp
Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe 2075 2080
2085 Ala Ala Gly Arg Lys Ser Leu Thr Leu Asn
Leu Ile Thr Glu Met 2090 2095 2100
Gly Arg Leu Pro Thr Phe Met Thr Gln Lys Ala Arg Asp Ala Leu
2105 2110 2115 Asp Asn
Leu Ala Val Leu His Thr Ala Glu Ala Gly Gly Arg Ala 2120
2125 2130 Tyr Asn His Ala Leu Ser Glu
Leu Pro Glu Thr Leu Glu Thr Leu 2135 2140
2145 Leu Leu Leu Thr Leu Leu Ala Thr Val Thr Gly Gly
Ile Phe Leu 2150 2155 2160
Phe Leu Met Ser Ala Arg Gly Ile Gly Lys Met Thr Leu Gly Met 2165
2170 2175 Cys Cys Ile Ile Thr
Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile 2180 2185
2190 Gln Pro His Trp Ile Ala Ala Ser Ile Ile
Leu Glu Phe Phe Leu 2195 2200 2205
Ile Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln
2210 2215 2220 Asp Asn
Gln Leu Thr Tyr Val Val Ile Ala Ile Leu Thr Val Val 2225
2230 2235 Ala Ala Thr Met Ala Asn Glu
Met Gly Phe Leu Glu Lys Thr Lys 2240 2245
2250 Lys Asp Leu Gly Leu Gly Ser Ile Ala Thr Gln Gln
Pro Glu Ser 2255 2260 2265
Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu 2270
2275 2280 Tyr Ala Val Ala Thr
Thr Phe Val Thr Pro Met Leu Arg His Ser 2285 2290
2295 Ile Glu Asn Ser Ser Val Asn Val Ser Leu
Thr Ala Ile Ala Asn 2300 2305 2310
Gln Ala Thr Val Leu Met Gly Leu Gly Lys Gly Trp Pro Leu Ser
2315 2320 2325 Lys Met
Asp Ile Gly Val Pro Leu Leu Ala Ile Gly Cys Tyr Ser 2330
2335 2340 Gln Val Asn Pro Ile Thr Leu
Thr Ala Ala Leu Phe Leu Leu Val 2345 2350
2355 Ala His Tyr Ala Ile Ile Gly Pro Gly Leu Gln Ala
Lys Ala Thr 2360 2365 2370
Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly Ile Met Lys Asn Pro 2375
2380 2385 Thr Val Asp Gly Ile
Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr 2390 2395
2400 Asp Pro Lys Phe Glu Lys Gln Leu Gly Gln
Val Met Leu Leu Val 2405 2410 2415
Leu Cys Val Thr Gln Val Leu Met Met Arg Thr Thr Trp Ala Leu
2420 2425 2430 Cys Glu
Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser Thr Leu Trp 2435
2440 2445 Glu Gly Asn Pro Gly Arg Phe
Trp Asn Thr Thr Ile Ala Val Ser 2450 2455
2460 Met Ala Asn Ile Phe Arg Gly Ser Tyr Leu Ala Gly
Ala Gly Leu 2465 2470 2475
Leu Phe Ser Ile Met Lys Asn Thr Thr Asn Thr Arg Arg Gly Thr 2480
2485 2490 Gly Asn Ile Gly Glu
Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu 2495 2500
2505 Asn Ala Leu Gly Lys Ser Glu Phe Gln Ile
Tyr Lys Lys Ser Gly 2510 2515 2520
Ile Gln Glu Val Asp Arg Thr Leu Ala Lys Glu Gly Ile Lys Arg
2525 2530 2535 Gly Glu
Thr Asp His His Ala Val Ser Arg Gly Ser Ala Lys Leu 2540
2545 2550 Arg Trp Phe Val Glu Arg Asn
Met Val Thr Pro Glu Gly Lys Val 2555 2560
2565 Val Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr
Tyr Cys Gly 2570 2575 2580
Gly Leu Lys Asn Val Arg Glu Val Lys Gly Leu Thr Lys Gly Gly 2585
2590 2595 Pro Gly His Glu Glu
Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn 2600 2605
2610 Leu Val Arg Leu Gln Ser Gly Val Asp Val
Phe Phe Ile Pro Pro 2615 2620 2625
Glu Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro
2630 2635 2640 Asn Pro
Thr Val Glu Ala Gly Arg Thr Leu Arg Val Leu Asn Leu 2645
2650 2655 Val Glu Asn Trp Leu Asn Asn
Asn Thr Gln Phe Cys Ile Lys Val 2660 2665
2670 Leu Asn Pro Tyr Met Pro Ser Val Ile Glu Lys Met
Glu Ala Leu 2675 2680 2685
Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg Asn Pro Leu Ser Arg 2690
2695 2700 Asn Ser Thr His Glu
Met Tyr Trp Val Ser Asn Ala Ser Gly Asn 2705 2710
2715 Ile Val Ser Ser Val Asn Met Ile Ser Arg
Met Leu Ile Asn Arg 2720 2725 2730
Phe Thr Met Arg Tyr Lys Lys Ala Thr Tyr Glu Pro Asp Val Asp
2735 2740 2745 Leu Gly
Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser Glu Ile Pro 2750
2755 2760 Asn Leu Asp Ile Ile Gly Lys
Arg Ile Glu Lys Ile Lys Gln Glu 2765 2770
2775 His Glu Thr Ser Trp His Tyr Asp Gln Asp His Pro
Tyr Lys Thr 2780 2785 2790
Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys Gln Thr Gly Ser Ala 2795
2800 2805 Ser Ser Met Val Asn
Gly Val Val Arg Leu Leu Thr Lys Pro Trp 2810 2815
2820 Asp Val Val Pro Met Val Thr Gln Met Ala
Met Thr Asp Thr Thr 2825 2830 2835
Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg
2840 2845 2850 Thr Gln
Glu Pro Lys Glu Gly Thr Lys Lys Leu Met Lys Ile Thr 2855
2860 2865 Ala Glu Trp Leu Trp Lys Glu
Leu Gly Lys Lys Lys Thr Pro Arg 2870 2875
2880 Met Cys Thr Arg Glu Glu Phe Thr Arg Lys Val Arg
Ser Asn Ala 2885 2890 2895
Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn Lys Trp Lys Ser Ala 2900
2905 2910 Arg Glu Ala Val Glu
Asp Ser Arg Phe Trp Glu Leu Val Asp Lys 2915 2920
2925 Glu Arg Asn Leu His Leu Glu Gly Lys Cys
Glu Thr Cys Val Tyr 2930 2935 2940
Asn Met Met Gly Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys
2945 2950 2955 Ala Lys
Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg 2960
2965 2970 Phe Leu Glu Phe Glu Ala Leu
Gly Phe Leu Asn Glu Asp His Trp 2975 2980
2985 Phe Ser Arg Glu Asn Ser Leu Ser Gly Val Glu Gly
Glu Gly Leu 2990 2995 3000
His Lys Leu Gly Tyr Ile Leu Arg Asp Val Ser Lys Lys Glu Gly 3005
3010 3015 Gly Ala Met Tyr Ala
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile 3020 3025
3030 Thr Leu Glu Asp Leu Lys Asn Glu Glu Met
Val Thr Asn His Met 3035 3040 3045
Glu Gly Glu His Lys Lys Leu Ala Glu Ala Ile Phe Lys Leu Thr
3050 3055 3060 Tyr Gln
Asn Lys Val Val Arg Val Gln Arg Pro Thr Pro Arg Gly 3065
3070 3075 Thr Val Met Asp Ile Ile Ser
Arg Arg Asp Gln Arg Gly Ser Gly 3080 3085
3090 Gln Val Gly Thr Tyr Gly Leu Asn Thr Phe Thr Asn
Met Glu Ala 3095 3100 3105
Gln Leu Ile Arg Gln Met Glu Gly Glu Gly Val Phe Lys Ser Ile 3110
3115 3120 Gln His Leu Thr Ile
Thr Glu Glu Ile Ala Val Gln Asn Trp Leu 3125 3130
3135 Ala Arg Val Gly Arg Glu Arg Leu Ser Arg
Met Ala Ile Ser Gly 3140 3145 3150
Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Ser Ala
3155 3160 3165 Leu Thr
Ala Leu Asn Asp Met Gly Lys Ile Arg Lys Asp Ile Gln 3170
3175 3180 Gln Trp Glu Pro Ser Arg Gly
Trp Asn Asp Trp Thr Gln Val Pro 3185 3190
3195 Phe Cys Ser His His Phe His Glu Leu Ile Met Lys
Asp Gly Arg 3200 3205 3210
Val Leu Val Val Pro Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg 3215
3220 3225 Ala Arg Ile Ser Gln
Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala 3230 3235
3240 Cys Leu Gly Lys Ser Tyr Ala Gln Met Trp
Ser Leu Met Tyr Phe 3245 3250 3255
His Arg Arg Asp Leu Arg Leu Ala Ala Asn Ala Ile Cys Ser Ala
3260 3265 3270 Val Pro
Ser His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser Ile 3275
3280 3285 His Ala Lys His Glu Trp Met
Thr Thr Glu Asp Met Leu Thr Val 3290 3295
3300 Trp Asn Arg Val Trp Ile Gln Glu Asn Pro Trp Met
Glu Asp Lys 3305 3310 3315
Thr Pro Val Glu Ser Trp Glu Glu Ile Pro Tyr Leu Gly Lys Arg 3320
3325 3330 Glu Asp Gln Trp Cys
Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala 3335 3340
3345 Thr Trp Ala Lys Asn Ile Gln Ala Ala Ile
Asn Gln Val Arg Ser 3350 3355 3360
Leu Ile Gly Asn Glu Glu Tyr Thr Asp Tyr Met Pro Ser Met Lys
3365 3370 3375 Arg Phe
Arg Arg Glu Glu Glu Glu Ala Gly Val Leu Trp 3380
3385 3390 1610723DNAArtificial SequenceDerived from
Dengue virus serotype 2, PDK-53 derivative, MVS 16agttgttagt
ctacgtggac cgacaaagac agattctttg agggagctaa gctcaatgta 60gttctaacag
ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg 120aaaaacacgc
ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag 180ctgacaaaga
gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg 240gccctggtgg
cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga 300tggggaacaa
ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt 360ggaaggatgc
tgaacatctt gaataggaga cgcagatctg caggcatgat cattatgctg 420attccaacag
tgatggcgtt ccatttaacc acacgtaacg gagaaccaca catgatcgtc 480agcagacaag
agaaagggaa aagtcttctg tttaaaacag aggttggcgt gaacatgtgt 540accctcatgg
ccatggacct tggtgaattg tgtgaagaca caatcacgta cgagtgtccc 600cttctcaggc
agaatgagcc agaagacata gactgttggt gcaactctac gtccacgtgg 660gtaacttatg
ggacgtgtac caccatggga gaacatagaa gagaaaaaag atcagtggca 720ctcgttccac
atgtgggaat gggactggag acacgaactg aaacatggat gtcatcagaa 780ggggcctgga
aacatgtcca gagaattgaa acttggatct tgagacatcc aggcttcacc 840atgatggcag
caatcctggc atacaccata ggaacgacac atttccaaag agccctgatc 900ttcatcttac
tgacagctgt cactccttca atgacaatgc gttgcatagg aatgtcaaat 960agagactttg
tggaaggggt ttcaggagga agctgggttg acatagtctt agaacatgga 1020agctgtgtga
cgacgatggc aaaaaacaaa ccaacattgg attttgaact gataaaaaca 1080gaagccaaac
agcctgccac cctaaggaag tactgtatag aggcaaagct aaccaacaca 1140acaacagaat
ctcgctgccc aacacaaggg gaacccagcc taaatgaaga gcaggacaaa 1200aggttcgtct
gcaaacactc catggtagac agaggatggg gaaatggatg tggactattt 1260ggaaagggag
gcattgtgac ctgtgctatg ttcagatgca aaaagaacat ggaaggaaaa 1320gttgtgcaac
cagaaaactt ggaatacacc attgtgataa cacctcactc aggggaagag 1380catgcagtcg
gaaatgacac aggaaaacat ggcaaggaaa tcaaaataac accacagagt 1440tccatcacag
aagcagaatt gacaggttat ggcactgtca caatggagtg ctctccaaga 1500acgggcctcg
acttcaatga gatggtgttg ctgcagatgg aaaataaagc ttggctggtg 1560cacaggcaat
ggttcctaga cctgccgtta ccatggttgc ccggagcgga cacacaaggg 1620tcaaattgga
tacagaaaga gacattggtc actttcaaaa atccccatgc gaagaaacag 1680gatgttgttg
ttttaggatc ccaagaaggg gccatgcaca cagcacttac aggggccaca 1740gaaatccaaa
tgtcatcagg aaacttactc ttcacaggac atctcaagtg caggctgaga 1800atggacaagc
tacagctcaa aggaatgtca tactctatgt gcacaggaaa gtttaaagtt 1860gtgaaggaaa
tagcagaaac acaacatgga acaatagtta tcagagtgca atatgaaggg 1920gacggctctc
catgcaagat cccttttgag ataatggatt tggaaaaaag acatgtctta 1980ggtcgcctga
ttacagtcaa cccaattgtg acagaaaaag atagcccagt caacatagaa 2040gcagaacctc
catttggaga cagctacatc atcataggag tagagccggg acaactgaag 2100ctcaactggt
ttaagaaagg aagttctatc ggccaaatgt ttgagacaac aatgaggggg 2160gcgaagagaa
tggccatttt aggtgacaca gcctgggatt ttggatcctt gggaggagtg 2220tttacatcta
taggaaaggc tctccaccaa gtctttggag caatctatgg agctgccttc 2280agtggggttt
catggactat gaaaatcctc ataggagtca ttatcacatg gataggaatg 2340aattcacgca
gcacctcact gtctgtgaca ctagtattgg tgggaattgt gacactgtat 2400ttgggagtca
tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa caaagaactg 2460aaatgtggca
gtgggatttt catcacagac aacgtgcaca catggacaga acaatacaag 2520ttccaaccag
aatccccttc aaaactagct tcagctatcc agaaagccca tgaagaggac 2580atttgtggaa
tccgctcagt aacaagactg gagaatctga tgtggaaaca aataacacca 2640gaattgaatc
acattctatc agaaaatgag gtgaagttaa ctattatgac aggagacatc 2700aaaggaatca
tgcaggcagg aaaacgatct ctgcggcctc agcccactga gctgaagtat 2760tcatggaaaa
catggggcaa agcaaaaatg ctctctacag agtctcataa ccagaccttt 2820ctcattgatg
gccccgaaac agcagaatgc cccaacacaa atagagcttg gaattcgttg 2880gaagttgaag
actatggctt tggagtattc accaccaata tatggctaaa attgaaagaa 2940aaacaggatg
tattctgcga ctcaaaactc atgtcagcgg ccataaaaga caacagagcc 3000gtccatgccg
atatgggtta ttggatagaa agtgcactca atgacacatg gaagatagag 3060aaagcctctt
tcattgaagt taaaaactgc cactggccaa aatcacacac cctctggagc 3120aatggagtgc
tagaaagtga gatgataatt ccaaagaatc tcgctggacc agtgtctcaa 3180cacaactata
gaccaggcta ccatacacaa ataacaggac catggcatct aggtaagctt 3240gagatggact
ttgatttctg tgatggaaca acagtggtag tgactgagga ctgcggaaat 3300agaggaccct
ctttgagaac aaccactgcc tctggaaaac tcataacaga atggtgctgc 3360cgatcttgca
cattaccacc gctaagatac agaggtgagg atgggtgctg gtacgggatg 3420gaaatcagac
cattgaagga gaaagaagag aatttggtca actccttggt cacagctgga 3480catgggcagg
tcgacaactt ttcactagga gtcttgggaa tggcattgtt cctggaggaa 3540atgcttagga
cccgagtagg aacgaaacat gcaatactac tagttgcagt ttcttttgtg 3600acattgatca
cagggaacat gtcctttaga gacctgggaa gagtgatggt tatggtaggc 3660gccactatga
cggatgacat aggtatgggc gtgacttatc ttgccctact agcagccttc 3720aaagtcagac
caacttttgc agctggacta ctcttgagaa agctgacctc caaggaattg 3780atgatgacta
ctataggaat tgtactcctc tcccagagca ccataccaga gaccattctt 3840gagttgactg
atgcgttagc cttaggcatg atggtcctca aaatggtgag aaatatggaa 3900aagtatcaat
tggcagtgac tatcatggct atcttgtgcg tcccaaacgc agtgatatta 3960caaaacgcat
ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc cccactgttc 4020ttaacatcct
cacagcaaaa aacagattgg ataccattag cattgacgat caaaggtctc 4080aatccaacag
ctatttttct aacaaccctc tcaagaacca gcaagaaaag gagctggcca 4140ttaaatgagg
ctatcatggc agtcgggatg gtgagcattt tagccagttc tctcctaaaa 4200aatgatattc
ccatgacagg accattagtg gctggagggc tcctcactgt gtgctacgtg 4260ctcactggac
gatcggccga tttggaactg gagagagcag ccgatgtcaa atgggaagac 4320caggcagaga
tatcaggaag cagtccaatc ctgtcaataa caatatcaga agatggtagc 4380atgtcgataa
aaaatgaaga ggaagaacaa acactgacca tactcattag aacaggattg 4440ctggtgatct
caggactttt tcctgtatca ataccaatca cggcagcagc atggtacctg 4500tgggaagtga
agaaacaacg ggccggagta ttgtgggatg ttccttcacc cccacccatg 4560ggaaaggctg
aactggaaga tggagcctat agaattaagc aaaaagggat tcttggatat 4620tcccagatcg
gagccggagt ttacaaagaa ggaacattcc atacaatgtg gcatgtcaca 4680cgtggcgctg
ttctaatgca taaaggaaag aggattgaac catcatgggc ggacgtcaag 4740aaagacctaa
tatcatatgg aggaggctgg aagttagaag gagaatggaa ggaaggagaa 4800gaagtccagg
tattggcact ggagcctgga aaaaatccaa gagccgtcca aacgaaacct 4860ggtcttttca
aaaccaacgc cggaacaata ggtgctgtat ctctggactt ttctcctgga 4920acgtcaggat
ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta tggtaatggt 4980gttgttacaa
ggagtggagc atatgtgagt gctatagccc agactgaaaa aagcattgaa 5040gacaacccag
agatcgaaga tgacattttc cgaaagagaa gactgaccat catggacctc 5100cacccaggag
cgggaaagac gaagagatac cttccggcca tagtcagaga agctataaaa 5160cggggtttga
gaacattaat cttggccccc actagagttg tggcagctga aatggaggaa 5220gcccttagag
gacttccaat aagataccag accccagcca tcagagctgt gcacaccggg 5280cgggagattg
tggacctaat gtgtcatgcc acatttacca tgaggctgct atcaccagtt 5340agagtgccaa
actacaacct gattatcatg gacgaagccc atttcacaga cccagcaagt 5400atagcagcta
gaggatacat ctcaactcga gtggagatgg gtgaggcagc tgggattttt 5460atgacagcca
ctcccccggg aagcagagac ccatttcctc agagcaatgc accaatcata 5520gatgaagaaa
gagaaatccc tgaacgctcg tggaattccg gacatgaatg ggtcacggat 5580tttaaaggga
agactgtttg gttcgttcca agtataaaag caggaaatga tatagcagct 5640tgcctgagga
aaaatggaaa gaaagtgata caactcagta ggaagacctt tgattctgag 5700tatgtcaaga
ctagaaccaa tgattgggac ttcgtggtta caactgacat ttcagaaatg 5760ggtgccaatt
tcaaggctga gagggttata gaccccagac gctgcatgaa accagtcata 5820ctaacagatg
gtgaagagcg ggtgattctg gcaggaccta tgccagtgac ccactctagt 5880gcagcacaaa
gaagagggag aataggaaga aatccaaaaa atgagaatga ccagtacata 5940tacatggggg
aacctctgga aaatgatgaa gactgtgcac actggaaaga agctaaaatg 6000ctcctagata
acatcaacac gccagaagga atcattccta gcatgttcga accagagcgt 6060gaaaaggtgg
atgccattga tggcgaatac cgcttgagag gagaagcaag gaaaaccttt 6120gtagacttaa
tgagaagagg agacctacca gtctggttgg cctacagagt ggcagctgaa 6180ggcatcaact
acgcagacag aaggtggtgt tttgatggag tcaagaacaa ccaaatccta 6240gaagaaaacg
tggaagttga aatctggaca aaagaagggg aaaggaagaa attgaaaccc 6300agatggttgg
atgctaggat ctattctgac ccactggcgc taaaagaatt taaggaattt 6360gcagccggaa
gaaagtctct gaccctgaac ctaatcacag aaatgggtag gctcccaacc 6420ttcatgactc
agaaggcaag agacgcactg gacaacttag cagtgctgca cacggctgag 6480gcaggtggaa
gggcgtacaa ccatgctctc agtgaactgc cggagaccct ggagacattg 6540cttttactga
cacttctggc tacagtcacg ggagggatct ttttattctt gatgagcgca 6600aggggcatag
ggaagatgac cctgggaatg tgctgcataa tcacggctag catcctccta 6660tggtacgcac
aaatacagcc acactggata gcagcttcaa taatactgga gttttttctc 6720atagttttgc
ttattccaga acctgaaaaa cagagaacac cccaagacaa ccaactgacc 6780tacgttgtca
tagccatcct cacagtggtg gccgcaacca tggcaaacga gatgggtttc 6840ctagaaaaaa
cgaagaaaga tctcggattg ggaagcattg caacccagca acccgagagc 6900aacatcctgg
acatagatct acgtcctgca tcagcatgga cgctgtatgc cgtggccaca 6960acatttgtta
caccaatgtt gagacatagc attgaaaatt cctcagtgaa tgtgtcccta 7020acagctatag
ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg gccattgtca 7080aagatggaca
tcggagttcc ccttctcgcc attggatgct actcacaagt caaccccata 7140actctcacag
cagctctttt cttattggta gcacattatg ccatcatagg gccaggactc 7200caagcaaaag
caaccagaga agctcagaaa agagcagcgg cgggcatcat gaaaaaccca 7260actgtcgatg
gaataacagt gattgaccta gatccaatac cttatgatcc aaagtttgaa 7320aagcagttgg
gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt gatgatgagg 7380actacatggg
ctctgtgtga ggctttaacc ttagctaccg ggcccatctc cacattgtgg 7440gaaggaaatc
cagggaggtt ttggaacact accattgcgg tgtcaatggc taacattttt 7500agagggagtt
acttggccgg agctggactt ctcttttcta ttatgaagaa cacaaccaac 7560acaagaaggg
gaactggcaa cataggagag acgcttggag agaaatggaa aagccgattg 7620aacgcattgg
gaaaaagtga attccagatc tacaagaaaa gtggaatcca ggaagtggat 7680agaaccttag
caaaagaagg cattaaaaga ggagaaacgg accatcacgc tgtgtcgcga 7740ggctcagcaa
aactgagatg gttcgttgag agaaacatgg tcacaccaga agggaaagta 7800gtggacctcg
gttgtggcag aggaggctgg tcatactatt gtggaggact aaagaatgta 7860agagaagtca
aaggcctaac aaaaggagga ccaggacacg aagaacccat ccccatgtca 7920acatatgggt
ggaatctagt gcgtcttcaa agtggagttg acgttttctt catcccgcca 7980gaaaagtgtg
acacattatt gtgtgacata ggggagtcat caccaaatcc cacagtggaa 8040gcaggacgaa
cactcagagt ccttaactta gtagaaaatt ggttgaacaa caacactcaa 8100ttttgcataa
aggttctcaa cccatatatg ccctcagtca tagaaaaaat ggaagcacta 8160caaaggaaat
atggaggagc cttagtgagg aatccactct cacgaaactc cacacatgag 8220atgtactggg
tatccaatgc ttccgggaac atagtgtcat cagtgaacat gatttcaagg 8280atgttgatca
acagatttac aatgagatac aagaaagcca cttacgagcc ggatgttgac 8340ctcggaagcg
gaacccgtaa catcgggatt gaaagtgaga taccaaacct agatataatt 8400gggaaaagaa
tagaaaaaat aaagcaagag catgaaacat catggcacta tgaccaagac 8460cacccataca
aaacgtgggc ataccatggt agctatgaaa caaaacagac tggatcagca 8520tcatccatgg
tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt cgtccccatg 8580gtgacacaga
tggcaatgac agacacgact ccatttggac aacagcgcgt ttttaaagag 8640aaagtggaca
cgagaaccca agaaccgaaa gaaggcacga agaaactaat gaaaataaca 8700gcagagtggc
tttggaaaga attagggaag aaaaagacac ccaggatgtg caccagagaa 8760gaattcacaa
gaaaggtgag aagcaatgca gccttggggg ccgtattcac tgatgagaac 8820aagtggaagt
cggcacgtga ggctgttgaa gatagtaggt tttgggagct ggttgacaag 8880gaaaggaatc
tccatcttga aggaaagtgt gaaacatgtg tgtacaacat gatgggaaaa 8940agagagaaga
agctagggga attcggcaag gcaaaaggca gcagagccat atggtacatg 9000tggcttggag
cacgcttctt agagtttgaa gccctaggat tcttaaatga agatcactgg 9060ttctccagag
agaactccct gagtggagtg gaaggagaag ggctgcacaa gctaggttac 9120attctaagag
acgtgagcaa gaaagaggga ggagcaatgt atgccgatga caccgcagga 9180tgggatacaa
gaatcacact agaagaccta aaaaatgaag aaatggtaac aaaccacatg 9240gaaggagaac
acaagaaact agccgaggcc attttcaaac taacgtacca aaacaaggtg 9300gtgcgtgtgc
aaagaccaac accaagaggc acagtaatgg acatcatatc gagaagagac 9360caaagaggta
gtggacaagt tggcacctat ggactcaata ctttcaccaa tatggaagcc 9420caactaatca
gacagatgga gggagaagga gtctttaaaa gcattcagca cctaacaatc 9480acagaagaaa
tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag gttatcaaga 9540atggccatca
gtggagatga ttgtgttgtg aaacctttag atgacaggtt cgcaagcgct 9600ttaacagctc
taaatgacat gggaaagatt aggaaagaca tacaacaatg ggaaccttca 9660agaggatgga
atgattggac acaagtgccc ttctgttcac accatttcca tgagttaatc 9720atgaaagacg
gtcgcgtact cgttgttcca tgtagaaacc aagatgaact gattggcaga 9780gcccgaatct
cccaaggagc agggtggtct ttgcgggaga cggcctgttt ggggaagtct 9840tacgcccaaa
tgtggagctt gatgtacttc cacagacgcg acctcaggct ggcggcaaat 9900gctatttgct
cggcagtacc atcacattgg gttccaacaa gtcgaacaac ctggtccata 9960catgctaaac
atgaatggat gacaacggaa gacatgctga cagtctggaa cagggtgtgg 10020attcaagaaa
acccatggat ggaagacaaa actccagtgg aatcatggga ggaaatccca 10080tacttgggga
aaagagaaga ccaatggtgc ggctcattga ttgggttaac aagcagggcc 10140acctgggcaa
agaacatcca agcagcaata aatcaagtta gatcccttat aggcaatgaa 10200gaatacacag
attacatgcc atccatgaaa agattcagaa gagaagagga agaagcagga 10260gttctgtggt
agaaagcaaa actaacatga aacaaggcta gaagtcaggt cggattaagc 10320catagtacgg
aaaaaactat gctacctgtg agccccgtcc aaggacgtta aaagaagtca 10380ggccatcata
aatgccatag cttgagtaaa ctatgcagcc tgtagctcca cctgagaagg 10440tgtaaaaaat
ccgggaggcc acaaaccatg gaagctgtac gcatggcgta gtggactagc 10500ggttagagga
gacccctccc ttacaaatcg cagcaacaat gggggcccaa ggcgagatga 10560agctgtagtc
tcgctggaag gactagaggt tagaggagac ccccccgaaa caaaaaacag 10620catattgacg
ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat tccaggcaca 10680gaacgccaga
aaatggaatg gtgctgttga atcaacaggt tct
10723173391PRTArtificial SequenceDerived from Dengue virus serotype 2,
PDK-53 derivative, MVS 17Met Asn Asn Gln Arg Lys Lys Ala Lys Asn Thr
Pro Phe Asn Met Leu 1 5 10
15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu Thr Lys Arg
20 25 30 Phe Ser
Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met 35
40 45 Ala Leu Val Ala Phe Leu Arg
Phe Leu Thr Ile Pro Pro Thr Ala Gly 50 55
60 Ile Leu Lys Arg Trp Gly Thr Ile Lys Lys Ser Lys
Ala Ile Asn Val 65 70 75
80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu Asn Ile Leu Asn
85 90 95 Arg Arg Arg
Arg Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val 100
105 110 Met Ala Phe His Leu Thr Thr Arg
Asn Gly Glu Pro His Met Ile Val 115 120
125 Ser Arg Gln Glu Lys Gly Lys Ser Leu Leu Phe Lys Thr
Glu Val Gly 130 135 140
Val Asn Met Cys Thr Leu Met Ala Met Asp Leu Gly Glu Leu Cys Glu 145
150 155 160 Asp Thr Ile Thr
Tyr Glu Cys Pro Leu Leu Arg Gln Asn Glu Pro Glu 165
170 175 Asp Ile Asp Cys Trp Cys Asn Ser Thr
Ser Thr Trp Val Thr Tyr Gly 180 185
190 Thr Cys Thr Thr Met Gly Glu His Arg Arg Glu Lys Arg Ser
Val Ala 195 200 205
Leu Val Pro His Val Gly Met Gly Leu Glu Thr Arg Thr Glu Thr Trp 210
215 220 Met Ser Ser Glu Gly
Ala Trp Lys His Val Gln Arg Ile Glu Thr Trp 225 230
235 240 Ile Leu Arg His Pro Gly Phe Thr Met Met
Ala Ala Ile Leu Ala Tyr 245 250
255 Thr Ile Gly Thr Thr His Phe Gln Arg Ala Leu Ile Phe Ile Leu
Leu 260 265 270 Thr
Ala Val Thr Pro Ser Met Thr Met Arg Cys Ile Gly Met Ser Asn 275
280 285 Arg Asp Phe Val Glu Gly
Val Ser Gly Gly Ser Trp Val Asp Ile Val 290 295
300 Leu Glu His Gly Ser Cys Val Thr Thr Met Ala
Lys Asn Lys Pro Thr 305 310 315
320 Leu Asp Phe Glu Leu Ile Lys Thr Glu Ala Lys Gln Pro Ala Thr Leu
325 330 335 Arg Lys
Tyr Cys Ile Glu Ala Lys Leu Thr Asn Thr Thr Thr Glu Ser 340
345 350 Arg Cys Pro Thr Gln Gly Glu
Pro Ser Leu Asn Glu Glu Gln Asp Lys 355 360
365 Arg Phe Val Cys Lys His Ser Met Val Asp Arg Gly
Trp Gly Asn Gly 370 375 380
Cys Gly Leu Phe Gly Lys Gly Gly Ile Val Thr Cys Ala Met Phe Arg 385
390 395 400 Cys Lys Lys
Asn Met Glu Gly Lys Val Val Gln Pro Glu Asn Leu Glu 405
410 415 Tyr Thr Ile Val Ile Thr Pro His
Ser Gly Glu Glu His Ala Val Gly 420 425
430 Asn Asp Thr Gly Lys His Gly Lys Glu Ile Lys Ile Thr
Pro Gln Ser 435 440 445
Ser Ile Thr Glu Ala Glu Leu Thr Gly Tyr Gly Thr Val Thr Met Glu 450
455 460 Cys Ser Pro Arg
Thr Gly Leu Asp Phe Asn Glu Met Val Leu Leu Gln 465 470
475 480 Met Glu Asn Lys Ala Trp Leu Val His
Arg Gln Trp Phe Leu Asp Leu 485 490
495 Pro Leu Pro Trp Leu Pro Gly Ala Asp Thr Gln Gly Ser Asn
Trp Ile 500 505 510
Gln Lys Glu Thr Leu Val Thr Phe Lys Asn Pro His Ala Lys Lys Gln
515 520 525 Asp Val Val Val
Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu 530
535 540 Thr Gly Ala Thr Glu Ile Gln Met
Ser Ser Gly Asn Leu Leu Phe Thr 545 550
555 560 Gly His Leu Lys Cys Arg Leu Arg Met Asp Lys Leu
Gln Leu Lys Gly 565 570
575 Met Ser Tyr Ser Met Cys Thr Gly Lys Phe Lys Val Val Lys Glu Ile
580 585 590 Ala Glu Thr
Gln His Gly Thr Ile Val Ile Arg Val Gln Tyr Glu Gly 595
600 605 Asp Gly Ser Pro Cys Lys Ile Pro
Phe Glu Ile Met Asp Leu Glu Lys 610 615
620 Arg His Val Leu Gly Arg Leu Ile Thr Val Asn Pro Ile
Val Thr Glu 625 630 635
640 Lys Asp Ser Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Asp Ser
645 650 655 Tyr Ile Ile Ile
Gly Val Glu Pro Gly Gln Leu Lys Leu Asn Trp Phe 660
665 670 Lys Lys Gly Ser Ser Ile Gly Gln Met
Phe Glu Thr Thr Met Arg Gly 675 680
685 Ala Lys Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe
Gly Ser 690 695 700
Leu Gly Gly Val Phe Thr Ser Ile Gly Lys Ala Leu His Gln Val Phe 705
710 715 720 Gly Ala Ile Tyr Gly
Ala Ala Phe Ser Gly Val Ser Trp Thr Met Lys 725
730 735 Ile Leu Ile Gly Val Ile Ile Thr Trp Ile
Gly Met Asn Ser Arg Ser 740 745
750 Thr Ser Leu Ser Val Thr Leu Val Leu Val Gly Ile Val Thr Leu
Tyr 755 760 765 Leu
Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys 770
775 780 Asn Lys Glu Leu Lys Cys
Gly Ser Gly Ile Phe Ile Thr Asp Asn Val 785 790
795 800 His Thr Trp Thr Glu Gln Tyr Lys Phe Gln Pro
Glu Ser Pro Ser Lys 805 810
815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu Glu Asp Ile Cys Gly Ile
820 825 830 Arg Ser
Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro 835
840 845 Glu Leu Asn His Ile Leu Ser
Glu Asn Glu Val Lys Leu Thr Ile Met 850 855
860 Thr Gly Asp Ile Lys Gly Ile Met Gln Ala Gly Lys
Arg Ser Leu Arg 865 870 875
880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala
885 890 895 Lys Met Leu
Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly 900
905 910 Pro Glu Thr Ala Glu Cys Pro Asn
Thr Asn Arg Ala Trp Asn Ser Leu 915 920
925 Glu Val Glu Asp Tyr Gly Phe Gly Val Phe Thr Thr Asn
Ile Trp Leu 930 935 940
Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys Leu Met Ser 945
950 955 960 Ala Ala Ile Lys
Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp 965
970 975 Ile Glu Ser Ala Leu Asn Asp Thr Trp
Lys Ile Glu Lys Ala Ser Phe 980 985
990 Ile Glu Val Lys Asn Cys His Trp Pro Lys Ser His Thr
Leu Trp Ser 995 1000 1005
Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro Lys Asn Leu Ala
1010 1015 1020 Gly Pro Val
Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln 1025
1030 1035 Ile Thr Gly Pro Trp His Leu Gly
Lys Leu Glu Met Asp Phe Asp 1040 1045
1050 Phe Cys Asp Gly Thr Thr Val Val Val Thr Glu Asp Cys
Gly Asn 1055 1060 1065
Arg Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile 1070
1075 1080 Thr Glu Trp Cys Cys
Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr 1085 1090
1095 Arg Gly Glu Asp Gly Cys Trp Tyr Gly Met
Glu Ile Arg Pro Leu 1100 1105 1110
Lys Glu Lys Glu Glu Asn Leu Val Asn Ser Leu Val Thr Ala Gly
1115 1120 1125 His Gly
Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala 1130
1135 1140 Leu Phe Leu Glu Glu Met Leu
Arg Thr Arg Val Gly Thr Lys His 1145 1150
1155 Ala Ile Leu Leu Val Ala Val Ser Phe Val Thr Leu
Ile Thr Gly 1160 1165 1170
Asn Met Ser Phe Arg Asp Leu Gly Arg Val Met Val Met Val Gly 1175
1180 1185 Ala Thr Met Thr Asp
Asp Ile Gly Met Gly Val Thr Tyr Leu Ala 1190 1195
1200 Leu Leu Ala Ala Phe Lys Val Arg Pro Thr
Phe Ala Ala Gly Leu 1205 1210 1215
Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu Met Met Thr Thr Ile
1220 1225 1230 Gly Ile
Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu 1235
1240 1245 Glu Leu Thr Asp Ala Leu Ala
Leu Gly Met Met Val Leu Lys Met 1250 1255
1260 Val Arg Asn Met Glu Lys Tyr Gln Leu Ala Val Thr
Ile Met Ala 1265 1270 1275
Ile Leu Cys Val Pro Asn Ala Val Ile Leu Gln Asn Ala Trp Lys 1280
1285 1290 Val Ser Cys Thr Ile
Leu Ala Val Val Ser Val Ser Pro Leu Phe 1295 1300
1305 Leu Thr Ser Ser Gln Gln Lys Thr Asp Trp
Ile Pro Leu Ala Leu 1310 1315 1320
Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile Phe Leu Thr Thr Leu
1325 1330 1335 Ser Arg
Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile 1340
1345 1350 Met Ala Val Gly Met Val Ser
Ile Leu Ala Ser Ser Leu Leu Lys 1355 1360
1365 Asn Asp Ile Pro Met Thr Gly Pro Leu Val Ala Gly
Gly Leu Leu 1370 1375 1380
Thr Val Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp Leu Glu Leu 1385
1390 1395 Glu Arg Ala Ala Asp
Val Lys Trp Glu Asp Gln Ala Glu Ile Ser 1400 1405
1410 Gly Ser Ser Pro Ile Leu Ser Ile Thr Ile
Ser Glu Asp Gly Ser 1415 1420 1425
Met Ser Ile Lys Asn Glu Glu Glu Glu Gln Thr Leu Thr Ile Leu
1430 1435 1440 Ile Arg
Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser 1445
1450 1455 Ile Pro Ile Thr Ala Ala Ala
Trp Tyr Leu Trp Glu Val Lys Lys 1460 1465
1470 Gln Arg Ala Gly Val Leu Trp Asp Val Pro Ser Pro
Pro Pro Met 1475 1480 1485
Gly Lys Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile Lys Gln Lys 1490
1495 1500 Gly Ile Leu Gly Tyr
Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu 1505 1510
1515 Gly Thr Phe His Thr Met Trp His Val Thr
Arg Gly Ala Val Leu 1520 1525 1530
Met His Lys Gly Lys Arg Ile Glu Pro Ser Trp Ala Asp Val Lys
1535 1540 1545 Lys Asp
Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu 1550
1555 1560 Trp Lys Glu Gly Glu Glu Val
Gln Val Leu Ala Leu Glu Pro Gly 1565 1570
1575 Lys Asn Pro Arg Ala Val Gln Thr Lys Pro Gly Leu
Phe Lys Thr 1580 1585 1590
Asn Ala Gly Thr Ile Gly Ala Val Ser Leu Asp Phe Ser Pro Gly 1595
1600 1605 Thr Ser Gly Ser Pro
Ile Ile Asp Lys Lys Gly Lys Val Val Gly 1610 1615
1620 Leu Tyr Gly Asn Gly Val Val Thr Arg Ser
Gly Ala Tyr Val Ser 1625 1630 1635
Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu Asp Asn Pro Glu Ile
1640 1645 1650 Glu Asp
Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu 1655
1660 1665 His Pro Gly Ala Gly Lys Thr
Lys Arg Tyr Leu Pro Ala Ile Val 1670 1675
1680 Arg Glu Ala Ile Lys Arg Gly Leu Arg Thr Leu Ile
Leu Ala Pro 1685 1690 1695
Thr Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly Leu 1700
1705 1710 Pro Ile Arg Tyr Gln
Thr Pro Ala Ile Arg Ala Val His Thr Gly 1715 1720
1725 Arg Glu Ile Val Asp Leu Met Cys His Ala
Thr Phe Thr Met Arg 1730 1735 1740
Leu Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Leu Ile Ile Met
1745 1750 1755 Asp Glu
Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly 1760
1765 1770 Tyr Ile Ser Thr Arg Val Glu
Met Gly Glu Ala Ala Gly Ile Phe 1775 1780
1785 Met Thr Ala Thr Pro Pro Gly Ser Arg Asp Pro Phe
Pro Gln Ser 1790 1795 1800
Asn Ala Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro Glu Arg Ser 1805
1810 1815 Trp Asn Ser Gly His
Glu Trp Val Thr Asp Phe Lys Gly Lys Thr 1820 1825
1830 Val Trp Phe Val Pro Ser Ile Lys Ala Gly
Asn Asp Ile Ala Ala 1835 1840 1845
Cys Leu Arg Lys Asn Gly Lys Lys Val Ile Gln Leu Ser Arg Lys
1850 1855 1860 Thr Phe
Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp 1865
1870 1875 Phe Val Val Thr Thr Asp Ile
Ser Glu Met Gly Ala Asn Phe Lys 1880 1885
1890 Ala Glu Arg Val Ile Asp Pro Arg Arg Cys Met Lys
Pro Val Ile 1895 1900 1905
Leu Thr Asp Gly Glu Glu Arg Val Ile Leu Ala Gly Pro Met Pro 1910
1915 1920 Val Thr His Ser Ser
Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg 1925 1930
1935 Asn Pro Lys Asn Glu Asn Asp Gln Tyr Ile
Tyr Met Gly Glu Pro 1940 1945 1950
Leu Glu Asn Asp Glu Asp Cys Ala His Trp Lys Glu Ala Lys Met
1955 1960 1965 Leu Leu
Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met 1970
1975 1980 Phe Glu Pro Glu Arg Glu Lys
Val Asp Ala Ile Asp Gly Glu Tyr 1985 1990
1995 Arg Leu Arg Gly Glu Ala Arg Lys Thr Phe Val Asp
Leu Met Arg 2000 2005 2010
Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Arg Val Ala Ala Glu 2015
2020 2025 Gly Ile Asn Tyr Ala
Asp Arg Arg Trp Cys Phe Asp Gly Val Lys 2030 2035
2040 Asn Asn Gln Ile Leu Glu Glu Asn Val Glu
Val Glu Ile Trp Thr 2045 2050 2055
Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro Arg Trp Leu Asp Ala
2060 2065 2070 Arg Ile
Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe 2075
2080 2085 Ala Ala Gly Arg Lys Ser Leu
Thr Leu Asn Leu Ile Thr Glu Met 2090 2095
2100 Gly Arg Leu Pro Thr Phe Met Thr Gln Lys Ala Arg
Asp Ala Leu 2105 2110 2115
Asp Asn Leu Ala Val Leu His Thr Ala Glu Ala Gly Gly Arg Ala 2120
2125 2130 Tyr Asn His Ala Leu
Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu 2135 2140
2145 Leu Leu Leu Thr Leu Leu Ala Thr Val Thr
Gly Gly Ile Phe Leu 2150 2155 2160
Phe Leu Met Ser Ala Arg Gly Ile Gly Lys Met Thr Leu Gly Met
2165 2170 2175 Cys Cys
Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile 2180
2185 2190 Gln Pro His Trp Ile Ala Ala
Ser Ile Ile Leu Glu Phe Phe Leu 2195 2200
2205 Ile Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg
Thr Pro Gln 2210 2215 2220
Asp Asn Gln Leu Thr Tyr Val Val Ile Ala Ile Leu Thr Val Val 2225
2230 2235 Ala Ala Thr Met Ala
Asn Glu Met Gly Phe Leu Glu Lys Thr Lys 2240 2245
2250 Lys Asp Leu Gly Leu Gly Ser Ile Ala Thr
Gln Gln Pro Glu Ser 2255 2260 2265
Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu
2270 2275 2280 Tyr Ala
Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser 2285
2290 2295 Ile Glu Asn Ser Ser Val Asn
Val Ser Leu Thr Ala Ile Ala Asn 2300 2305
2310 Gln Ala Thr Val Leu Met Gly Leu Gly Lys Gly Trp
Pro Leu Ser 2315 2320 2325
Lys Met Asp Ile Gly Val Pro Leu Leu Ala Ile Gly Cys Tyr Ser 2330
2335 2340 Gln Val Asn Pro Ile
Thr Leu Thr Ala Ala Leu Phe Leu Leu Val 2345 2350
2355 Ala His Tyr Ala Ile Ile Gly Pro Gly Leu
Gln Ala Lys Ala Thr 2360 2365 2370
Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly Ile Met Lys Asn Pro
2375 2380 2385 Thr Val
Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr 2390
2395 2400 Asp Pro Lys Phe Glu Lys Gln
Leu Gly Gln Val Met Leu Leu Val 2405 2410
2415 Leu Cys Val Thr Gln Val Leu Met Met Arg Thr Thr
Trp Ala Leu 2420 2425 2430
Cys Glu Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser Thr Leu Trp 2435
2440 2445 Glu Gly Asn Pro Gly
Arg Phe Trp Asn Thr Thr Ile Ala Val Ser 2450 2455
2460 Met Ala Asn Ile Phe Arg Gly Ser Tyr Leu
Ala Gly Ala Gly Leu 2465 2470 2475
Leu Phe Ser Ile Met Lys Asn Thr Thr Asn Thr Arg Arg Gly Thr
2480 2485 2490 Gly Asn
Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu 2495
2500 2505 Asn Ala Leu Gly Lys Ser Glu
Phe Gln Ile Tyr Lys Lys Ser Gly 2510 2515
2520 Ile Gln Glu Val Asp Arg Thr Leu Ala Lys Glu Gly
Ile Lys Arg 2525 2530 2535
Gly Glu Thr Asp His His Ala Val Ser Arg Gly Ser Ala Lys Leu 2540
2545 2550 Arg Trp Phe Val Glu
Arg Asn Met Val Thr Pro Glu Gly Lys Val 2555 2560
2565 Val Asp Leu Gly Cys Gly Arg Gly Gly Trp
Ser Tyr Tyr Cys Gly 2570 2575 2580
Gly Leu Lys Asn Val Arg Glu Val Lys Gly Leu Thr Lys Gly Gly
2585 2590 2595 Pro Gly
His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn 2600
2605 2610 Leu Val Arg Leu Gln Ser Gly
Val Asp Val Phe Phe Ile Pro Pro 2615 2620
2625 Glu Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu
Ser Ser Pro 2630 2635 2640
Asn Pro Thr Val Glu Ala Gly Arg Thr Leu Arg Val Leu Asn Leu 2645
2650 2655 Val Glu Asn Trp Leu
Asn Asn Asn Thr Gln Phe Cys Ile Lys Val 2660 2665
2670 Leu Asn Pro Tyr Met Pro Ser Val Ile Glu
Lys Met Glu Ala Leu 2675 2680 2685
Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg Asn Pro Leu Ser Arg
2690 2695 2700 Asn Ser
Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn 2705
2710 2715 Ile Val Ser Ser Val Asn Met
Ile Ser Arg Met Leu Ile Asn Arg 2720 2725
2730 Phe Thr Met Arg Tyr Lys Lys Ala Thr Tyr Glu Pro
Asp Val Asp 2735 2740 2745
Leu Gly Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser Glu Ile Pro 2750
2755 2760 Asn Leu Asp Ile Ile
Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu 2765 2770
2775 His Glu Thr Ser Trp His Tyr Asp Gln Asp
His Pro Tyr Lys Thr 2780 2785 2790
Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys Gln Thr Gly Ser Ala
2795 2800 2805 Ser Ser
Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp 2810
2815 2820 Asp Val Val Pro Met Val Thr
Gln Met Ala Met Thr Asp Thr Thr 2825 2830
2835 Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val
Asp Thr Arg 2840 2845 2850
Thr Gln Glu Pro Lys Glu Gly Thr Lys Lys Leu Met Lys Ile Thr 2855
2860 2865 Ala Glu Trp Leu Trp
Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg 2870 2875
2880 Met Cys Thr Arg Glu Glu Phe Thr Arg Lys
Val Arg Ser Asn Ala 2885 2890 2895
Ala Leu Gly Ala Val Phe Thr Asp Glu Asn Lys Trp Lys Ser Ala
2900 2905 2910 Arg Glu
Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys 2915
2920 2925 Glu Arg Asn Leu His Leu Glu
Gly Lys Cys Glu Thr Cys Val Tyr 2930 2935
2940 Asn Met Met Gly Lys Arg Glu Lys Lys Leu Gly Glu
Phe Gly Lys 2945 2950 2955
Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg 2960
2965 2970 Phe Leu Glu Phe Glu
Ala Leu Gly Phe Leu Asn Glu Asp His Trp 2975 2980
2985 Phe Ser Arg Glu Asn Ser Leu Ser Gly Val
Glu Gly Glu Gly Leu 2990 2995 3000
His Lys Leu Gly Tyr Ile Leu Arg Asp Val Ser Lys Lys Glu Gly
3005 3010 3015 Gly Ala
Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile 3020
3025 3030 Thr Leu Glu Asp Leu Lys Asn
Glu Glu Met Val Thr Asn His Met 3035 3040
3045 Glu Gly Glu His Lys Lys Leu Ala Glu Ala Ile Phe
Lys Leu Thr 3050 3055 3060
Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Thr Pro Arg Gly 3065
3070 3075 Thr Val Met Asp Ile
Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly 3080 3085
3090 Gln Val Gly Thr Tyr Gly Leu Asn Thr Phe
Thr Asn Met Glu Ala 3095 3100 3105
Gln Leu Ile Arg Gln Met Glu Gly Glu Gly Val Phe Lys Ser Ile
3110 3115 3120 Gln His
Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu 3125
3130 3135 Ala Arg Val Gly Arg Glu Arg
Leu Ser Arg Met Ala Ile Ser Gly 3140 3145
3150 Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe
Ala Ser Ala 3155 3160 3165
Leu Thr Ala Leu Asn Asp Met Gly Lys Ile Arg Lys Asp Ile Gln 3170
3175 3180 Gln Trp Glu Pro Ser
Arg Gly Trp Asn Asp Trp Thr Gln Val Pro 3185 3190
3195 Phe Cys Ser His His Phe His Glu Leu Ile
Met Lys Asp Gly Arg 3200 3205 3210
Val Leu Val Val Pro Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg
3215 3220 3225 Ala Arg
Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala 3230
3235 3240 Cys Leu Gly Lys Ser Tyr Ala
Gln Met Trp Ser Leu Met Tyr Phe 3245 3250
3255 His Arg Arg Asp Leu Arg Leu Ala Ala Asn Ala Ile
Cys Ser Ala 3260 3265 3270
Val Pro Ser His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser Ile 3275
3280 3285 His Ala Lys His Glu
Trp Met Thr Thr Glu Asp Met Leu Thr Val 3290 3295
3300 Trp Asn Arg Val Trp Ile Gln Glu Asn Pro
Trp Met Glu Asp Lys 3305 3310 3315
Thr Pro Val Glu Ser Trp Glu Glu Ile Pro Tyr Leu Gly Lys Arg
3320 3325 3330 Glu Asp
Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala 3335
3340 3345 Thr Trp Ala Lys Asn Ile Gln
Ala Ala Ile Asn Gln Val Arg Ser 3350 3355
3360 Leu Ile Gly Asn Glu Glu Tyr Thr Asp Tyr Met Pro
Ser Met Lys 3365 3370 3375
Arg Phe Arg Arg Glu Glu Glu Glu Ala Gly Val Leu Trp 3380
3385 3390 1810717DNAArtificial SequenceDerived
from Dengue virus serotype 2/Dengue virus serotype 3, MVS
18agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaatgta
60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg
120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag
180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg
240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga
300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt
360ggaaggatgc tgaacatctt gaataggaga cgcagatctg caggcatgat cattatgctg
420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gagagccgcg catgattgtg
480gggaagaatg aaagaggaaa atccctactt ttcaagacag cctctggaat caacatgtgc
540acactcatag ctatggatct gggagagatg tgtgatgaca cggtcactta caaatgcccc
600cacattaccg aagtggagcc tgaagacatt gactgctggt gcaaccttac atcgacatgg
660gtgacttatg gaacatgcaa tcaagctgga gagcatagac gcgataagag atcagtggcg
720ttagctcccc atgttggcat gggactggac acacgcactc aaacctggat gtcggctgaa
780ggagcttgga gacaagtcga gaaggtagag acatgggccc ttaggcaccc agggtttacc
840atactagccc tatttcttgc ccattacata ggcacttcct tgacccagaa agtggttatt
900tttatactat taatgctggt taccccatcc atgacaatga gatgtgtagg agtaggaaac
960agagattttg tggaaggcct atcgggagct acgtgggttg acgtggtgct cgagcacggt
1020gggtgtgtga ctaccatggc taagaacaag cccacgctgg acatagagct tcagaagacc
1080gaggccaccc aactggcgac cctaaggaag ctatgcattg agggaaaaat taccaacata
1140acaaccgact caagatgtcc cacccaaggg gaagcgattt tacctgagga gcaggaccag
1200aactacgtgt gtaagcatac atacgtggac agaggctggg gaaacggttg tggtttgttt
1260ggcaagggaa gcttggtgac atgcgcgaaa tttcaatgtt tagaatcaat agagggaaaa
1320gtggtgcaac atgagaacct caaatacacc gtcatcatca cagtgcacac aggagaccaa
1380caccaggtgg gaaatgaaac gcagggagtc acggctgaga taacacccca ggcatcaacc
1440gctgaagcca ttttacctga atatggaacc ctcgggctag aatgctcacc acggacaggt
1500ttggatttca atgaaatgat ctcattgaca atgaagaaca aagcatggat ggtacataga
1560caatggttct ttgacttacc cctaccatgg acatcaggag cttcagcaga aacaccaact
1620tggaacagga aagagcttct tgtgacattt aaaaatgcac atgcaaaaaa gcaagaagta
1680gttgttcttg gatcacaaga gggagcaatg catacagcac tgacaggagc tacagagatc
1740caaacctcag gaggcacaag tatctttgcg gggcacttaa aatgtagact caagatggac
1800aaattggaac tcaaggggat gagctatgca atgtgcttga gtagctttgt gttgaagaaa
1860gaagtctccg aaacgcagca tgggacaata ctcattaagg ttgagtacaa aggggaagat
1920gcaccctgca agattccttt ctccacggag gatggacaag gaaaagctct caatggcaga
1980ctgatcacag ccaatccagt ggtgaccaag aaggaggagc ctgtcaacat tgaggctgaa
2040cctccttttg gagaaagtaa catagtaatt ggaattggag acaaagccct gaaaatcaac
2100tggtacaaga agggaagctc gattgggaag atgttcgagg ccactgccag aggtgcaagg
2160cgcatggcca tcttgggaga cacagcctgg gactttggat cagtgggtgg tgttttgaat
2220tcattaggga aaatggtcca ccaaatattt gggagtgctt acacagccct atttggtgga
2280gtctcctgga tgatgaaaat tggaataggt gtcctcttaa cctggatagg gttgaactca
2340aaaaatactt ctatgtcatt ttcatgcatc gcggccggca ttgtgacact gtatttggga
2400gtcatggtgc aggccgatag tggttgcgtt gtgagctgga aaaacaaaga actgaaatgt
2460ggcagtggga ttttcatcac agacaacgtg cacacatgga cagaacaata caagttccaa
2520ccagaatccc cttcaaaact agcttcagct atccagaaag cccatgaaga ggacatttgt
2580ggaatccgct cagtaacaag actggagaat ctgatgtgga aacaaataac accagaattg
2640aatcacattc tatcagaaaa tgaggtgaag ttaactatta tgacaggaga catcaaagga
2700atcatgcagg caggaaaacg atctctgcgg cctcagccca ctgagctgaa gtattcatgg
2760aaaacatggg gcaaagcaaa aatgctctct acagagtctc ataaccagac ctttctcatt
2820gatggccccg aaacagcaga atgccccaac acaaatagag cttggaattc gttggaagtt
2880gaagactatg gctttggagt attcaccacc aatatatggc taaaattgaa agaaaaacag
2940gatgtattct gcgactcaaa actcatgtca gcggccataa aagacaacag agccgtccat
3000gccgatatgg gttattggat agaaagtgca ctcaatgaca catggaagat agagaaagcc
3060tctttcattg aagttaaaaa ctgccactgg ccaaaatcac acaccctctg gagcaatgga
3120gtgctagaaa gtgagatgat aattccaaag aatctcgctg gaccagtgtc tcaacacaac
3180tatagaccag gctaccatac acaaataaca ggaccatggc atctaggtaa gcttgagatg
3240gactttgatt tctgtgatgg aacaacagtg gtagtgactg aggactgcgg aaatagagga
3300ccctctttga gaacaaccac tgcctctgga aaactcataa cagaatggtg ctgccgatct
3360tgcacattac caccgctaag atacagaggt gaggatgggt gctggtacgg gatggaaatc
3420agaccattga aggagaaaga agagaatttg gtcaactcct tggtcacagc tggacatggg
3480caggtcgaca acttttcact aggagtcttg ggaatggcat tgttcctgga ggaaatgctt
3540aggacccgag taggaacgaa acatgcaata ctactagttg cagtttcttt tgtgacattg
3600atcacaggga acatgtcctt tagagacctg ggaagagtga tggttatggt aggcgccact
3660atgacggatg acataggtat gggcgtgact tatcttgccc tactagcagc cttcaaagtc
3720agaccaactt ttgcagctgg actactcttg agaaagctga cctccaagga attgatgatg
3780actactatag gaattgtact cctctcccag agcaccatac cagagaccat tcttgagttg
3840actgatgcgt tagccttagg catgatggtc ctcaaaatgg tgagaaatat ggaaaagtat
3900caattggcag tgactatcat ggctatcttg tgcgtcccaa acgcagtgat attacaaaac
3960gcatggaaag tgagttgcac aatattggca gtggtgtccg tttccccact gttcttaaca
4020tcctcacagc aaaaaacaga ttggatacca ttagcattga cgatcaaagg tctcaatcca
4080acagctattt ttctaacaac cctctcaaga accagcaaga aaaggagctg gccattaaat
4140gaggctatca tggcagtcgg gatggtgagc attttagcca gttctctcct aaaaaatgat
4200attcccatga caggaccatt agtggctgga gggctcctca ctgtgtgcta cgtgctcact
4260ggacgatcgg ccgatttgga actggagaga gcagccgatg tcaaatggga agaccaggca
4320gagatatcag gaagcagtcc aatcctgtca ataacaatat cagaagatgg tagcatgtcg
4380ataaaaaatg aagaggaaga acaaacactg accatactca ttagaacagg attgctggtg
4440atctcaggac tttttcctgt atcaatacca atcacggcag cagcatggta cctgtgggaa
4500gtgaagaaac aacgggccgg agtattgtgg gatgttcctt cacccccacc catgggaaag
4560gctgaactgg aagatggagc ctatagaatt aagcaaaaag ggattcttgg atattcccag
4620atcggagccg gagtttacaa agaaggaaca ttccatacaa tgtggcatgt cacacgtggc
4680gctgttctaa tgcataaagg aaagaggatt gaaccatcat gggcggacgt caagaaagac
4740ctaatatcat atggaggagg ctggaagtta gaaggagaat ggaaggaagg agaagaagtc
4800caggtattgg cactggagcc tggaaaaaat ccaagagccg tccaaacgaa acctggtctt
4860ttcaaaacca acgccggaac aataggtgct gtatctctgg acttttctcc tggaacgtca
4920ggatctccaa ttatcgacaa aaaaggaaaa gttgtgggtc tttatggtaa tggtgttgtt
4980acaaggagtg gagcatatgt gagtgctata gcccagactg aaaaaagcat tgaagacaac
5040ccagagatcg aagatgacat tttccgaaag agaagactga ccatcatgga cctccaccca
5100ggagcgggaa agacgaagag ataccttccg gccatagtca gagaagctat aaaacggggt
5160ttgagaacat taatcttggc ccccactaga gttgtggcag ctgaaatgga ggaagccctt
5220agaggacttc caataagata ccagacccca gccatcagag ctgtgcacac cgggcgggag
5280attgtggacc taatgtgtca tgccacattt accatgaggc tgctatcacc agttagagtg
5340ccaaactaca acctgattat catggacgaa gcccatttca cagacccagc aagtatagca
5400gctagaggat acatctcaac tcgagtggag atgggtgagg cagctgggat ttttatgaca
5460gccactcccc cgggaagcag agacccattt cctcagagca atgcaccaat catagatgaa
5520gaaagagaaa tccctgaacg ctcgtggaat tccggacatg aatgggtcac ggattttaaa
5580gggaagactg tttggttcgt tccaagtata aaagcaggaa atgatatagc agcttgcctg
5640aggaaaaatg gaaagaaagt gatacaactc agtaggaaga cctttgattc tgagtatgtc
5700aagactagaa ccaatgattg ggacttcgtg gttacaactg acatttcaga aatgggtgcc
5760aatttcaagg ctgagagggt tatagacccc agacgctgca tgaaaccagt catactaaca
5820gatggtgaag agcgggtgat tctggcagga cctatgccag tgacccactc tagtgcagca
5880caaagaagag ggagaatagg aagaaatcca aaaaatgaga atgaccagta catatacatg
5940ggggaacctc tggaaaatga tgaagactgt gcacactgga aagaagctaa aatgctccta
6000gataacatca acacgccaga aggaatcatt cctagcatgt tcgaaccaga gcgtgaaaag
6060gtggatgcca ttgatggcga ataccgcttg agaggagaag caaggaaaac ctttgtagac
6120ttaatgagaa gaggagacct accagtctgg ttggcctaca gagtggcagc tgaaggcatc
6180aactacgcag acagaaggtg gtgttttgat ggagtcaaga acaaccaaat cctagaagaa
6240aacgtggaag ttgaaatctg gacaaaagaa ggggaaagga agaaattgaa acccagatgg
6300ttggatgcta ggatctattc tgacccactg gcgctaaaag aatttaagga atttgcagcc
6360ggaagaaagt ctctgaccct gaacctaatc acagaaatgg gtaggctccc aaccttcatg
6420actcagaagg caagagacgc actggacaac ttagcagtgc tgcacacggc tgaggcaggt
6480ggaagggcgt acaaccatgc tctcagtgaa ctgccggaga ccctggagac attgctttta
6540ctgacacttc tggctacagt cacgggaggg atctttttat tcttgatgag cgcaaggggc
6600atagggaaga tgaccctggg aatgtgctgc ataatcacgg ctagcatcct cctatggtac
6660gcacaaatac agccacactg gatagcagct tcaataatac tggagttttt tctcatagtt
6720ttgcttattc cagaacctga aaaacagaga acaccccaag acaaccaact gacctacgtt
6780gtcatagcca tcctcacagt ggtggccgca accatggcaa acgagatggg tttcctagaa
6840aaaacgaaga aagatctcgg attgggaagc attgcaaccc agcaacccga gagcaacatc
6900ctggacatag atctacgtcc tgcatcagca tggacgctgt atgccgtggc cacaacattt
6960gttacaccaa tgttgagaca tagcattgaa aattcctcag tgaatgtgtc cctaacagct
7020atagccaacc aagccacagt gttaatgggt ctcgggaaag gatggccatt gtcaaagatg
7080gacatcggag ttccccttct cgccattgga tgctactcac aagtcaaccc cataactctc
7140acagcagctc ttttcttatt ggtagcacat tatgccatca tagggccagg actccaagca
7200aaagcaacca gagaagctca gaaaagagca gcggcgggca tcatgaaaaa cccaactgtc
7260gatggaataa cagtgattga cctagatcca ataccttatg atccaaagtt tgaaaagcag
7320ttgggacaag taatgctcct agtcctctgc gtgactcaag tattgatgat gaggactaca
7380tgggctctgt gtgaggcttt aaccttagct accgggccca tctccacatt gtgggaagga
7440aatccaggga ggttttggaa cactaccatt gcggtgtcaa tggctaacat ttttagaggg
7500agttacttgg ccggagctgg acttctcttt tctattatga agaacacaac caacacaaga
7560aggggaactg gcaacatagg agagacgctt ggagagaaat ggaaaagccg attgaacgcg
7620ttgggaaaaa gtgaattcca gatctacaag aaaagtggaa tccaggaagt ggatagaacc
7680ttagcaaaag aaggcattaa aagaggagaa acggaccatc acgctgtgtc gcgaggctca
7740gcaaaactga gatggttcgt tgagagaaac atggtcacac cagaagggaa agtagtggac
7800ctcggttgtg gcagaggagg ctggtcatac tattgtggag gactaaagaa tgtaagagaa
7860gtcaaaggcc taacaaaagg aggaccagga cacgaagaac ccatccccat gtcaacatat
7920gggtggaatc tagtgcgtct tcaaagtgga gttgacgttt tcttcatccc gccagaaaag
7980tgtgacacat tattgtgtga cataggggag tcatcaccaa atcccacagt ggaagcagga
8040cgaacactca gagtccttaa cttagtagaa aattggttga acaacaacac tcaattttgc
8100ataaaggttc tcaacccata tatgccctca gtcatagaaa aaatggaagc actacaaagg
8160aaatatggag gagccttagt gaggaatcca ctctcacgaa actccacaca tgagatgtac
8220tgggtatcca atgcttccgg gaacatagtg tcatcagtga acatgatttc aaggatgttg
8280atcaacagat ttacaatgag atacaagaaa gccacttacg agccggatgt tgacctcgga
8340agcggaaccc gtaacatcgg gattgaaagt gagataccaa acctagatat aattgggaaa
8400agaatagaaa aaataaagca agagcatgaa acatcatggc actatgacca agaccaccca
8460tacaaaacgt gggcatacca tggtagctat gaaacaaaac agactggatc agcatcatcc
8520atggtcaacg gagtggtcag gctgctgaca aaaccttggg acgtcgtccc catggtgaca
8580cagatggcaa tgacagacac gactccattt ggacaacagc gcgtttttaa agagaaagtg
8640gacacgagaa cccaagaacc gaaagaaggc acgaagaaac taatgaaaat aacagcagag
8700tggctttgga aagaattagg gaagaaaaag acacccagga tgtgcaccag agaagaattc
8760acaagaaagg tgagaagcaa tgcagccttg ggggccatat tcactgatga gaacaagtgg
8820aagtcggcac gtgaggctgt tgaagatagt aggttttggg agctggttga caaggaaagg
8880aatctccatc ttgaaggaaa gtgtgaaaca tgtgtgtaca acatgatggg aaaaagagag
8940aagaagctag gggaattcgg caaggcaaaa ggcagcagag ccatatggta catgtggctt
9000ggagcacgct tcttagagtt tgaagcccta ggattcttaa atgaagatca ctggttctcc
9060agagagaact ccctgagtgg agtggaagga gaagggctgc acaagctagg ttacattcta
9120agagacgtga gcaagaaaga gggaggagca atgtatgccg atgacaccgc aggatgggat
9180acaagaatca cactagaaga cctaaaaaat gaagaaatgg taacaaacca catggaagga
9240gaacacaaga aactagccga ggccattttc aaactaacgt accaaaacaa ggtggtgcgt
9300gtgcaaagac caacaccaag aggcacagta atggacatca tatcgagaag agaccaaaga
9360ggtagtggac aagttggcac ctatggactc aatactttca ccaatatgga agcccaacta
9420atcagacaga tggagggaga aggagtcttt aaaagcattc agcacctaac aatcacagaa
9480gaaatcgctg tgcaaaactg gttagcaaga gtggggcgcg aaaggttatc aagaatggcc
9540atcagtggag atgattgtgt tgtgaaacct ttagatgaca ggttcgcaag cgctttaaca
9600gctctaaatg acatgggaaa gattaggaaa gacatacaac aatgggaacc ttcaagagga
9660tggaatgatt ggacacaagt gcccttctgt tcacaccatt tccatgagtt aatcatgaaa
9720gacggtcgcg tactcgttgt tccatgtaga aaccaagatg aactgattgg cagagcccga
9780atctcccaag gagcagggtg gtctttgcgg gagacggcct gtttggggaa gtcttacgcc
9840caaatgtgga gcttgatgta cttccacaga cgcgacctca ggctggcggc aaatgctatt
9900tgctcggcag taccatcaca ttgggttcca acaagtcgaa caacctggtc catacatgct
9960aaacatgaat ggatgacaac ggaagacatg ctgacagtct ggaacagggt gtggattcaa
10020gaaaacccat ggatggaaga caaaactcca gtggaatcat gggaggaaat cccatacttg
10080gggaaaagag aagaccaatg gtgcggctca ttgattgggt taacaagcag ggccacctgg
10140gcaaagaaca tccaagcagc aataaatcaa gttagatccc ttataggcaa tgaagaatac
10200acagattaca tgccatccat gaaaagattc agaagagaag aggaagaagc aggagttctg
10260tggtagaaag caaaactaac atgaaacaag gctagaagtc aggtcggatt aagccatagt
10320acggaaaaaa ctatgctacc tgtgagcccc gtccaaggac gttaaaagaa gtcaggccat
10380cataaatgcc atagcttgag taaactatgc agcctgtagc tccacctgag aaggtgtaaa
10440aaatccggga ggccacaaac catggaagct gtacgcatgg cgtagtggac tagcggttag
10500aggagacccc tcccttacaa atcgcagcaa caatgggggc ccaaggcgag atgaagctgt
10560agtctcgctg gaaggactag aggttagagg agaccccccc gaaacaaaaa acagcatatt
10620gacgctggga aagaccagag atcctgctgt ctcctcagca tcattccagg cacagaacgc
10680cagaaaatgg aatggtgctg ttgaatcaac aggttct
10717193389PRTArtificial SequenceDerived from Dengue virus serotype
2/Dengue virus serotype 3, MVS 19Met Asn Asn Gln Arg Lys Lys Ala Lys
Asn Thr Pro Phe Asn Met Leu 1 5 10
15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu Thr
Lys Arg 20 25 30
Phe Ser Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met
35 40 45 Ala Leu Val Ala
Phe Leu Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly 50
55 60 Ile Leu Lys Arg Trp Gly Thr Ile
Lys Lys Ser Lys Ala Ile Asn Val 65 70
75 80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu
Asn Ile Leu Asn 85 90
95 Arg Arg Arg Arg Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val
100 105 110 Met Ala Phe
His Leu Thr Thr Arg Asp Gly Glu Pro Arg Met Ile Val 115
120 125 Gly Lys Asn Glu Arg Gly Lys Ser
Leu Leu Phe Lys Thr Ala Ser Gly 130 135
140 Ile Asn Met Cys Thr Leu Ile Ala Met Asp Leu Gly Glu
Met Cys Asp 145 150 155
160 Asp Thr Val Thr Tyr Lys Cys Pro His Ile Thr Glu Val Glu Pro Glu
165 170 175 Asp Ile Asp Cys
Trp Cys Asn Leu Thr Ser Thr Trp Val Thr Tyr Gly 180
185 190 Thr Cys Asn Gln Ala Gly Glu His Arg
Arg Asp Lys Arg Ser Val Ala 195 200
205 Leu Ala Pro His Val Gly Met Gly Leu Asp Thr Arg Thr Gln
Thr Trp 210 215 220
Met Ser Ala Glu Gly Ala Trp Arg Gln Val Glu Lys Val Glu Thr Trp 225
230 235 240 Ala Leu Arg His Pro
Gly Phe Thr Ile Leu Ala Leu Phe Leu Ala His 245
250 255 Tyr Ile Gly Thr Ser Leu Thr Gln Lys Val
Val Ile Phe Ile Leu Leu 260 265
270 Met Leu Val Thr Pro Ser Met Thr Met Arg Cys Val Gly Val Gly
Asn 275 280 285 Arg
Asp Phe Val Glu Gly Leu Ser Gly Ala Thr Trp Val Asp Val Val 290
295 300 Leu Glu His Gly Gly Cys
Val Thr Thr Met Ala Lys Asn Lys Pro Thr 305 310
315 320 Leu Asp Ile Glu Leu Gln Lys Thr Glu Ala Thr
Gln Leu Ala Thr Leu 325 330
335 Arg Lys Leu Cys Ile Glu Gly Lys Ile Thr Asn Ile Thr Thr Asp Ser
340 345 350 Arg Cys
Pro Thr Gln Gly Glu Ala Ile Leu Pro Glu Glu Gln Asp Gln 355
360 365 Asn Tyr Val Cys Lys His Thr
Tyr Val Asp Arg Gly Trp Gly Asn Gly 370 375
380 Cys Gly Leu Phe Gly Lys Gly Ser Leu Val Thr Cys
Ala Lys Phe Gln 385 390 395
400 Cys Leu Glu Ser Ile Glu Gly Lys Val Val Gln His Glu Asn Leu Lys
405 410 415 Tyr Thr Val
Ile Ile Thr Val His Thr Gly Asp Gln His Gln Val Gly 420
425 430 Asn Glu Thr Gln Gly Val Thr Ala
Glu Ile Thr Pro Gln Ala Ser Thr 435 440
445 Ala Glu Ala Ile Leu Pro Glu Tyr Gly Thr Leu Gly Leu
Glu Cys Ser 450 455 460
Pro Arg Thr Gly Leu Asp Phe Asn Glu Met Ile Ser Leu Thr Met Lys 465
470 475 480 Asn Lys Ala Trp
Met Val His Arg Gln Trp Phe Phe Asp Leu Pro Leu 485
490 495 Pro Trp Thr Ser Gly Ala Ser Ala Glu
Thr Pro Thr Trp Asn Arg Lys 500 505
510 Glu Leu Leu Val Thr Phe Lys Asn Ala His Ala Lys Lys Gln
Glu Val 515 520 525
Val Val Leu Gly Ser Gln Glu Gly Ala Met His Thr Ala Leu Thr Gly 530
535 540 Ala Thr Glu Ile Gln
Thr Ser Gly Gly Thr Ser Ile Phe Ala Gly His 545 550
555 560 Leu Lys Cys Arg Leu Lys Met Asp Lys Leu
Glu Leu Lys Gly Met Ser 565 570
575 Tyr Ala Met Cys Leu Ser Ser Phe Val Leu Lys Lys Glu Val Ser
Glu 580 585 590 Thr
Gln His Gly Thr Ile Leu Ile Lys Val Glu Tyr Lys Gly Glu Asp 595
600 605 Ala Pro Cys Lys Ile Pro
Phe Ser Thr Glu Asp Gly Gln Gly Lys Ala 610 615
620 Leu Asn Gly Arg Leu Ile Thr Ala Asn Pro Val
Val Thr Lys Lys Glu 625 630 635
640 Glu Pro Val Asn Ile Glu Ala Glu Pro Pro Phe Gly Glu Ser Asn Ile
645 650 655 Val Ile
Gly Ile Gly Asp Lys Ala Leu Lys Ile Asn Trp Tyr Lys Lys 660
665 670 Gly Ser Ser Ile Gly Lys Met
Phe Glu Ala Thr Ala Arg Gly Ala Arg 675 680
685 Arg Met Ala Ile Leu Gly Asp Thr Ala Trp Asp Phe
Gly Ser Val Gly 690 695 700
Gly Val Leu Asn Ser Leu Gly Lys Met Val His Gln Ile Phe Gly Ser 705
710 715 720 Ala Tyr Thr
Ala Leu Phe Gly Gly Val Ser Trp Met Met Lys Ile Gly 725
730 735 Ile Gly Val Leu Leu Thr Trp Ile
Gly Leu Asn Ser Lys Asn Thr Ser 740 745
750 Met Ser Phe Ser Cys Ile Ala Ala Gly Ile Val Thr Leu
Tyr Leu Gly 755 760 765
Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys Asn Lys 770
775 780 Glu Leu Lys Cys
Gly Ser Gly Ile Phe Ile Thr Asp Asn Val His Thr 785 790
795 800 Trp Thr Glu Gln Tyr Lys Phe Gln Pro
Glu Ser Pro Ser Lys Leu Ala 805 810
815 Ser Ala Ile Gln Lys Ala His Glu Glu Asp Ile Cys Gly Ile
Arg Ser 820 825 830
Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro Glu Leu
835 840 845 Asn His Ile Leu
Ser Glu Asn Glu Val Lys Leu Thr Ile Met Thr Gly 850
855 860 Asp Ile Lys Gly Ile Met Gln Ala
Gly Lys Arg Ser Leu Arg Pro Gln 865 870
875 880 Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly
Lys Ala Lys Met 885 890
895 Leu Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly Pro Glu
900 905 910 Thr Ala Glu
Cys Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu Glu Val 915
920 925 Glu Asp Tyr Gly Phe Gly Val Phe
Thr Thr Asn Ile Trp Leu Lys Leu 930 935
940 Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys Leu Met
Ser Ala Ala 945 950 955
960 Ile Lys Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp Ile Glu
965 970 975 Ser Ala Leu Asn
Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe Ile Glu 980
985 990 Val Lys Asn Cys His Trp Pro Lys
Ser His Thr Leu Trp Ser Asn Gly 995 1000
1005 Val Leu Glu Ser Glu Met Ile Ile Pro Lys Asn
Leu Ala Gly Pro 1010 1015 1020
Val Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln Ile Thr
1025 1030 1035 Gly Pro Trp
His Leu Gly Lys Leu Glu Met Asp Phe Asp Phe Cys 1040
1045 1050 Asp Gly Thr Thr Val Val Val Thr
Glu Asp Cys Gly Asn Arg Gly 1055 1060
1065 Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile
Thr Glu 1070 1075 1080
Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr Arg Gly 1085
1090 1095 Glu Asp Gly Cys Trp
Tyr Gly Met Glu Ile Arg Pro Leu Lys Glu 1100 1105
1110 Lys Glu Glu Asn Leu Val Asn Ser Leu Val
Thr Ala Gly His Gly 1115 1120 1125
Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala Leu Phe
1130 1135 1140 Leu Glu
Glu Met Leu Arg Thr Arg Val Gly Thr Lys His Ala Ile 1145
1150 1155 Leu Leu Val Ala Val Ser Phe
Val Thr Leu Ile Thr Gly Asn Met 1160 1165
1170 Ser Phe Arg Asp Leu Gly Arg Val Met Val Met Val
Gly Ala Thr 1175 1180 1185
Met Thr Asp Asp Ile Gly Met Gly Val Thr Tyr Leu Ala Leu Leu 1190
1195 1200 Ala Ala Phe Lys Val
Arg Pro Thr Phe Ala Ala Gly Leu Leu Leu 1205 1210
1215 Arg Lys Leu Thr Ser Lys Glu Leu Met Met
Thr Thr Ile Gly Ile 1220 1225 1230
Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu Glu Leu
1235 1240 1245 Thr Asp
Ala Leu Ala Leu Gly Met Met Val Leu Lys Met Val Arg 1250
1255 1260 Asn Met Glu Lys Tyr Gln Leu
Ala Val Thr Ile Met Ala Ile Leu 1265 1270
1275 Cys Val Pro Asn Ala Val Ile Leu Gln Asn Ala Trp
Lys Val Ser 1280 1285 1290
Cys Thr Ile Leu Ala Val Val Ser Val Ser Pro Leu Phe Leu Thr 1295
1300 1305 Ser Ser Gln Gln Lys
Thr Asp Trp Ile Pro Leu Ala Leu Thr Ile 1310 1315
1320 Lys Gly Leu Asn Pro Thr Ala Ile Phe Leu
Thr Thr Leu Ser Arg 1325 1330 1335
Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile Met Ala
1340 1345 1350 Val Gly
Met Val Ser Ile Leu Ala Ser Ser Leu Leu Lys Asn Asp 1355
1360 1365 Ile Pro Met Thr Gly Pro Leu
Val Ala Gly Gly Leu Leu Thr Val 1370 1375
1380 Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp Leu Glu
Leu Glu Arg 1385 1390 1395
Ala Ala Asp Val Lys Trp Glu Asp Gln Ala Glu Ile Ser Gly Ser 1400
1405 1410 Ser Pro Ile Leu Ser
Ile Thr Ile Ser Glu Asp Gly Ser Met Ser 1415 1420
1425 Ile Lys Asn Glu Glu Glu Glu Gln Thr Leu
Thr Ile Leu Ile Arg 1430 1435 1440
Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser Ile Pro
1445 1450 1455 Ile Thr
Ala Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys Gln Arg 1460
1465 1470 Ala Gly Val Leu Trp Asp Val
Pro Ser Pro Pro Pro Met Gly Lys 1475 1480
1485 Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile Lys Gln
Lys Gly Ile 1490 1495 1500
Leu Gly Tyr Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu Gly Thr 1505
1510 1515 Phe His Thr Met Trp
His Val Thr Arg Gly Ala Val Leu Met His 1520 1525
1530 Lys Gly Lys Arg Ile Glu Pro Ser Trp Ala
Asp Val Lys Lys Asp 1535 1540 1545
Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu Trp Lys
1550 1555 1560 Glu Gly
Glu Glu Val Gln Val Leu Ala Leu Glu Pro Gly Lys Asn 1565
1570 1575 Pro Arg Ala Val Gln Thr Lys
Pro Gly Leu Phe Lys Thr Asn Ala 1580 1585
1590 Gly Thr Ile Gly Ala Val Ser Leu Asp Phe Ser Pro
Gly Thr Ser 1595 1600 1605
Gly Ser Pro Ile Ile Asp Lys Lys Gly Lys Val Val Gly Leu Tyr 1610
1615 1620 Gly Asn Gly Val Val
Thr Arg Ser Gly Ala Tyr Val Ser Ala Ile 1625 1630
1635 Ala Gln Thr Glu Lys Ser Ile Glu Asp Asn
Pro Glu Ile Glu Asp 1640 1645 1650
Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu His Pro
1655 1660 1665 Gly Ala
Gly Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val Arg Glu 1670
1675 1680 Ala Ile Lys Arg Gly Leu Arg
Thr Leu Ile Leu Ala Pro Thr Arg 1685 1690
1695 Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly
Leu Pro Ile 1700 1705 1710
Arg Tyr Gln Thr Pro Ala Ile Arg Ala Val His Thr Gly Arg Glu 1715
1720 1725 Ile Val Asp Leu Met
Cys His Ala Thr Phe Thr Met Arg Leu Leu 1730 1735
1740 Ser Pro Val Arg Val Pro Asn Tyr Asn Leu
Ile Ile Met Asp Glu 1745 1750 1755
Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly Tyr Ile
1760 1765 1770 Ser Thr
Arg Val Glu Met Gly Glu Ala Ala Gly Ile Phe Met Thr 1775
1780 1785 Ala Thr Pro Pro Gly Ser Arg
Asp Pro Phe Pro Gln Ser Asn Ala 1790 1795
1800 Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro Glu Arg
Ser Trp Asn 1805 1810 1815
Ser Gly His Glu Trp Val Thr Asp Phe Lys Gly Lys Thr Val Trp 1820
1825 1830 Phe Val Pro Ser Ile
Lys Ala Gly Asn Asp Ile Ala Ala Cys Leu 1835 1840
1845 Arg Lys Asn Gly Lys Lys Val Ile Gln Leu
Ser Arg Lys Thr Phe 1850 1855 1860
Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp Phe Val
1865 1870 1875 Val Thr
Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys Ala Glu 1880
1885 1890 Arg Val Ile Asp Pro Arg Arg
Cys Met Lys Pro Val Ile Leu Thr 1895 1900
1905 Asp Gly Glu Glu Arg Val Ile Leu Ala Gly Pro Met
Pro Val Thr 1910 1915 1920
His Ser Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg Asn Pro 1925
1930 1935 Lys Asn Glu Asn Asp
Gln Tyr Ile Tyr Met Gly Glu Pro Leu Glu 1940 1945
1950 Asn Asp Glu Asp Cys Ala His Trp Lys Glu
Ala Lys Met Leu Leu 1955 1960 1965
Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met Phe Glu
1970 1975 1980 Pro Glu
Arg Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr Arg Leu 1985
1990 1995 Arg Gly Glu Ala Arg Lys Thr
Phe Val Asp Leu Met Arg Arg Gly 2000 2005
2010 Asp Leu Pro Val Trp Leu Ala Tyr Arg Val Ala Ala
Glu Gly Ile 2015 2020 2025
Asn Tyr Ala Asp Arg Arg Trp Cys Phe Asp Gly Val Lys Asn Asn 2030
2035 2040 Gln Ile Leu Glu Glu
Asn Val Glu Val Glu Ile Trp Thr Lys Glu 2045 2050
2055 Gly Glu Arg Lys Lys Leu Lys Pro Arg Trp
Leu Asp Ala Arg Ile 2060 2065 2070
Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe Ala Ala
2075 2080 2085 Gly Arg
Lys Ser Leu Thr Leu Asn Leu Ile Thr Glu Met Gly Arg 2090
2095 2100 Leu Pro Thr Phe Met Thr Gln
Lys Ala Arg Asp Ala Leu Asp Asn 2105 2110
2115 Leu Ala Val Leu His Thr Ala Glu Ala Gly Gly Arg
Ala Tyr Asn 2120 2125 2130
His Ala Leu Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu Leu Leu 2135
2140 2145 Leu Thr Leu Leu Ala
Thr Val Thr Gly Gly Ile Phe Leu Phe Leu 2150 2155
2160 Met Ser Ala Arg Gly Ile Gly Lys Met Thr
Leu Gly Met Cys Cys 2165 2170 2175
Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile Gln Pro
2180 2185 2190 His Trp
Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu Ile Val 2195
2200 2205 Leu Leu Ile Pro Glu Pro Glu
Lys Gln Arg Thr Pro Gln Asp Asn 2210 2215
2220 Gln Leu Thr Tyr Val Val Ile Ala Ile Leu Thr Val
Val Ala Ala 2225 2230 2235
Thr Met Ala Asn Glu Met Gly Phe Leu Glu Lys Thr Lys Lys Asp 2240
2245 2250 Leu Gly Leu Gly Ser
Ile Ala Thr Gln Gln Pro Glu Ser Asn Ile 2255 2260
2265 Leu Asp Ile Asp Leu Arg Pro Ala Ser Ala
Trp Thr Leu Tyr Ala 2270 2275 2280
Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser Ile Glu
2285 2290 2295 Asn Ser
Ser Val Asn Val Ser Leu Thr Ala Ile Ala Asn Gln Ala 2300
2305 2310 Thr Val Leu Met Gly Leu Gly
Lys Gly Trp Pro Leu Ser Lys Met 2315 2320
2325 Asp Ile Gly Val Pro Leu Leu Ala Ile Gly Cys Tyr
Ser Gln Val 2330 2335 2340
Asn Pro Ile Thr Leu Thr Ala Ala Leu Phe Leu Leu Val Ala His 2345
2350 2355 Tyr Ala Ile Ile Gly
Pro Gly Leu Gln Ala Lys Ala Thr Arg Glu 2360 2365
2370 Ala Gln Lys Arg Ala Ala Ala Gly Ile Met
Lys Asn Pro Thr Val 2375 2380 2385
Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr Asp Pro
2390 2395 2400 Lys Phe
Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val Leu Cys 2405
2410 2415 Val Thr Gln Val Leu Met Met
Arg Thr Thr Trp Ala Leu Cys Glu 2420 2425
2430 Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser Thr Leu
Trp Glu Gly 2435 2440 2445
Asn Pro Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser Met Ala 2450
2455 2460 Asn Ile Phe Arg Gly
Ser Tyr Leu Ala Gly Ala Gly Leu Leu Phe 2465 2470
2475 Ser Ile Met Lys Asn Thr Thr Asn Thr Arg
Arg Gly Thr Gly Asn 2480 2485 2490
Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu Asn Ala
2495 2500 2505 Leu Gly
Lys Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly Ile Gln 2510
2515 2520 Glu Val Asp Arg Thr Leu Ala
Lys Glu Gly Ile Lys Arg Gly Glu 2525 2530
2535 Thr Asp His His Ala Val Ser Arg Gly Ser Ala Lys
Leu Arg Trp 2540 2545 2550
Phe Val Glu Arg Asn Met Val Thr Pro Glu Gly Lys Val Val Asp 2555
2560 2565 Leu Gly Cys Gly Arg
Gly Gly Trp Ser Tyr Tyr Cys Gly Gly Leu 2570 2575
2580 Lys Asn Val Arg Glu Val Lys Gly Leu Thr
Lys Gly Gly Pro Gly 2585 2590 2595
His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn Leu Val
2600 2605 2610 Arg Leu
Gln Ser Gly Val Asp Val Phe Phe Ile Pro Pro Glu Lys 2615
2620 2625 Cys Asp Thr Leu Leu Cys Asp
Ile Gly Glu Ser Ser Pro Asn Pro 2630 2635
2640 Thr Val Glu Ala Gly Arg Thr Leu Arg Val Leu Asn
Leu Val Glu 2645 2650 2655
Asn Trp Leu Asn Asn Asn Thr Gln Phe Cys Ile Lys Val Leu Asn 2660
2665 2670 Pro Tyr Met Pro Ser
Val Ile Glu Lys Met Glu Ala Leu Gln Arg 2675 2680
2685 Lys Tyr Gly Gly Ala Leu Val Arg Asn Pro
Leu Ser Arg Asn Ser 2690 2695 2700
Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn Ile Val
2705 2710 2715 Ser Ser
Val Asn Met Ile Ser Arg Met Leu Ile Asn Arg Phe Thr 2720
2725 2730 Met Arg Tyr Lys Lys Ala Thr
Tyr Glu Pro Asp Val Asp Leu Gly 2735 2740
2745 Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser Glu Ile
Pro Asn Leu 2750 2755 2760
Asp Ile Ile Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu His Glu 2765
2770 2775 Thr Ser Trp His Tyr
Asp Gln Asp His Pro Tyr Lys Thr Trp Ala 2780 2785
2790 Tyr His Gly Ser Tyr Glu Thr Lys Gln Thr
Gly Ser Ala Ser Ser 2795 2800 2805
Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp Asp Val
2810 2815 2820 Val Pro
Met Val Thr Gln Met Ala Met Thr Asp Thr Thr Pro Phe 2825
2830 2835 Gly Gln Gln Arg Val Phe Lys
Glu Lys Val Asp Thr Arg Thr Gln 2840 2845
2850 Glu Pro Lys Glu Gly Thr Lys Lys Leu Met Lys Ile
Thr Ala Glu 2855 2860 2865
Trp Leu Trp Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg Met Cys 2870
2875 2880 Thr Arg Glu Glu Phe
Thr Arg Lys Val Arg Ser Asn Ala Ala Leu 2885 2890
2895 Gly Ala Ile Phe Thr Asp Glu Asn Lys Trp
Lys Ser Ala Arg Glu 2900 2905 2910
Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys Glu Arg
2915 2920 2925 Asn Leu
His Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr Asn Met 2930
2935 2940 Met Gly Lys Arg Glu Lys Lys
Leu Gly Glu Phe Gly Lys Ala Lys 2945 2950
2955 Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala
Arg Phe Leu 2960 2965 2970
Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp Phe Ser 2975
2980 2985 Arg Glu Asn Ser Leu
Ser Gly Val Glu Gly Glu Gly Leu His Lys 2990 2995
3000 Leu Gly Tyr Ile Leu Arg Asp Val Ser Lys
Lys Glu Gly Gly Ala 3005 3010 3015
Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile Thr Leu
3020 3025 3030 Glu Asp
Leu Lys Asn Glu Glu Met Val Thr Asn His Met Glu Gly 3035
3040 3045 Glu His Lys Lys Leu Ala Glu
Ala Ile Phe Lys Leu Thr Tyr Gln 3050 3055
3060 Asn Lys Val Val Arg Val Gln Arg Pro Thr Pro Arg
Gly Thr Val 3065 3070 3075
Met Asp Ile Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly Gln Val 3080
3085 3090 Gly Thr Tyr Gly Leu
Asn Thr Phe Thr Asn Met Glu Ala Gln Leu 3095 3100
3105 Ile Arg Gln Met Glu Gly Glu Gly Val Phe
Lys Ser Ile Gln His 3110 3115 3120
Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu Ala Arg
3125 3130 3135 Val Gly
Arg Glu Arg Leu Ser Arg Met Ala Ile Ser Gly Asp Asp 3140
3145 3150 Cys Val Val Lys Pro Leu Asp
Asp Arg Phe Ala Ser Ala Leu Thr 3155 3160
3165 Ala Leu Asn Asp Met Gly Lys Ile Arg Lys Asp Ile
Gln Gln Trp 3170 3175 3180
Glu Pro Ser Arg Gly Trp Asn Asp Trp Thr Gln Val Pro Phe Cys 3185
3190 3195 Ser His His Phe His
Glu Leu Ile Met Lys Asp Gly Arg Val Leu 3200 3205
3210 Val Val Pro Cys Arg Asn Gln Asp Glu Leu
Ile Gly Arg Ala Arg 3215 3220 3225
Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala Cys Leu
3230 3235 3240 Gly Lys
Ser Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe His Arg 3245
3250 3255 Arg Asp Leu Arg Leu Ala Ala
Asn Ala Ile Cys Ser Ala Val Pro 3260 3265
3270 Ser His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser
Ile His Ala 3275 3280 3285
Lys His Glu Trp Met Thr Thr Glu Asp Met Leu Thr Val Trp Asn 3290
3295 3300 Arg Val Trp Ile Gln
Glu Asn Pro Trp Met Glu Asp Lys Thr Pro 3305 3310
3315 Val Glu Ser Trp Glu Glu Ile Pro Tyr Leu
Gly Lys Arg Glu Asp 3320 3325 3330
Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala Thr Trp
3335 3340 3345 Ala Lys
Asn Ile Gln Ala Ala Ile Asn Gln Val Arg Ser Leu Ile 3350
3355 3360 Gly Asn Glu Glu Tyr Thr Asp
Tyr Met Pro Ser Met Lys Arg Phe 3365 3370
3375 Arg Arg Glu Glu Glu Glu Ala Gly Val Leu Trp
3380 3385 2010723DNAArtificial
SequenceDerived from Dengue virus serotype 2/Dengue virus serotype
4, MVS 20agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa
gctcaatgta 60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg
gaaaaaggcg 120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac
tgtgcaacag 180ctgacaaaga gattctcact tggaatgctg cagggacgag gacctttaaa
actgttcatg 240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat
attgaagaga 300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag
gaaagagatt 360ggaaggatgc tgaacatctt gaataggaga cgcagctctg caggcatgat
cattatgctg 420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gcgaacccct
catgatagtg 480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat
caacaaatgc 540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta
taaatgcccc 600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac
gtctacctgg 660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg
ctcagtagct 720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat
gtcatcggaa 780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc
aggattcgcg 840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg
aactgtcttc 900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg
agtaggaaac 960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct
agaacatgga 1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact
gactaagaca 1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat
atcaaacata 1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga
acaagaccaa 1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg
tggcttgttt 1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat
aacaggcaat 1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa
tggagacacc 1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac
tcccaggtca 1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg
tgaacccagg 1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac
atggcttgtg 1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga
cacatcagag 1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc
caagagacag 1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc
tggagccaca 1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg
caaagtccgt 1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa
gttctcaatt 1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa
gtatgaaggt 1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga
aaaagtggtt 1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac
caacatagag 2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag
tgcattaaca 2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac
atacagaggt 2160gcaaaacgaa tggccattct aggtgaaaca gcttgggatt ttggttccgt
tggtggactg 2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac
aaccctgttt 2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg
gattggcacg 2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt
gacactgtat 2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa
caaagaactg 2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga
acaatacaag 2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca
tgaagaggac 2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca
aataacacca 2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac
aggagacatc 2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga
gctgaagtat 2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa
ccagaccttt 2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg
gaattcgttg 2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa
attgaaagaa 2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga
caacagagcc 3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg
gaagatagag 3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac
cctctggagc 3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc
agtgtctcaa 3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct
aggtaagctt 3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga
ctgcggaaat 3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga
atggtgctgc 3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg
gtacgggatg 3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt
cacagctgga 3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt
cctggaggaa 3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt
ttcttttgtg 3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt
tatggtaggc 3660gccactatga cgggtgacat aggtatgggc gtgacttatc ttgccctact
agcagccttc 3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc
cagggaattg 3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga
gaccattctt 3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag
aaatatggaa 3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc
agtgatatta 3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc
cccactgttc 4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat
caaaggtctc 4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag
gagctggcca 4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc
tctcctaaaa 4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt
gtgctacgtg 4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa
atgggaagac 4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga
agatggtagc 4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag
aacaggattg 4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc
atggtacctg 4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc
cccacccatg 4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat
tcttggatat 4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg
gcatgtcaca 4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc
ggacgtcaag 4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa
ggaaggagaa 4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca
aacgaaacct 4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt
ttctcctgga 4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta
tggtaatggt 4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa
aagcattgaa 5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat
catggacctc 5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga
agctataaaa 5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga
aatggaggaa 5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt
gcacaccggg 5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct
atcaccagtt 5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga
tccagcaagt 5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc
tgggattttt 5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc
accaatcata 5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg
ggtcacggat 5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga
tatagcagct 5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt
tgattctgag 5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat
ttcagaaatg 5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa
accagtcata 5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac
ccactctagt 5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga
ccagtacata 5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga
agctaaaatg 6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga
accagagcgt 6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag
gaaaaccttt 6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt
ggcagctgaa 6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa
ccaaatccta 6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa
attgaaaccc 6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt
taaggaattt 6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag
gctcccaacc 6420ttcatgactc agaaggtaag agacgcactg gacaacttag cagtgctgca
cacggctgag 6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct
ggagacattg 6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt
gatgagcgca 6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag
catcctccta 6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga
gttttttctc 6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa
ccaactgacc 6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga
gatgggtttc 6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca
acccgagagc 6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc
cgtggccaca 6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa
tgtgtcccta 7020acagccatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg
gccattgtca 7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt
caaccccata 7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg
gccaggactc 7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat
gaaaaaccca 7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc
aaagtttgaa 7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt
gatgatgagg 7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc
cacattgtgg 7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc
taacattttt 7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa
cacaaccaac 7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa
aagccgattg 7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca
ggaagtggat 7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc
tgtgtcgcga 7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga
agggaaagta 7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact
aaagaatgta 7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat
ccccatgtca 7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt
catcccgcca 7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc
cacagtggaa 8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa
caacactcaa 8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat
ggaagcacta 8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc
cacacatgag 8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat
gatttcaagg 8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc
ggatgttgac 8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct
agatataatt 8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta
tgaccaagac 8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac
tggatcagca 8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt
cgtccccatg 8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt
ttttaaagag 8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat
gaaaataaca 8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg
caccagagaa 8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac
tgatgagaac 8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct
ggttgacaag 8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat
gatgggaaaa 8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat
atggtacatg 9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga
agatcactgg 9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa
gctaggttac 9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga
caccgcagga 9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac
aaaccacatg 9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca
aaacaaggtg 9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc
gagaagagac 9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa
tatggaagcc 9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca
cctaacaatc 9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag
gttatcaaga 9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt
cgcaagcgct 9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg
ggaaccttca 9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca
tgagttaatc 9720atgaaagacg gtcgcgtact cgttgttccc tgtagaaacc aagatgaact
gattggcaga 9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt
ggggaagtct 9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct
ggcggcaaat 9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac
ctggtccata 9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa
cagggtgtgg 10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga
ggaaatccca 10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac
aagcagggcc 10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat
aggcaatgaa 10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga
agaagcagga 10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt
cggattaagc 10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta
aaagaagtca 10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca
cctgagaagg 10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta
gtggactagc 10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa
ggcgagatga 10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa
caaaaaacag 10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat
tccaggcaca 10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tct
10723213391PRTArtificial SequenceDerived from Dengue virus
serotype 2/Dengue virus serotype 4, MVS 21Met Asn Asn Gln Arg Lys
Lys Ala Lys Asn Thr Pro Phe Asn Met Leu 1 5
10 15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln
Gln Leu Thr Lys Arg 20 25
30 Phe Ser Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe
Met 35 40 45 Ala
Leu Val Ala Phe Leu Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly 50
55 60 Ile Leu Lys Arg Trp Gly
Thr Ile Lys Lys Ser Lys Ala Ile Asn Val 65 70
75 80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met
Leu Asn Ile Leu Asn 85 90
95 Arg Arg Arg Ser Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val
100 105 110 Met Ala
Phe His Leu Thr Thr Arg Asp Gly Glu Pro Leu Met Ile Val 115
120 125 Ala Lys His Glu Arg Gly Arg
Pro Leu Leu Phe Lys Thr Thr Glu Gly 130 135
140 Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly
Glu Met Cys Glu 145 150 155
160 Asp Thr Val Thr Tyr Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu
165 170 175 Asp Ile Asp
Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Met Tyr Gly 180
185 190 Thr Cys Thr Gln Ser Gly Glu Arg
Arg Arg Glu Lys Arg Ser Val Ala 195 200
205 Leu Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala
Glu Thr Trp 210 215 220
Met Ser Ser Glu Gly Ala Trp Lys His Ala Gln Arg Val Glu Ser Trp 225
230 235 240 Ile Leu Arg Asn
Pro Gly Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr 245
250 255 Met Ile Gly Gln Thr Gly Ile Gln Arg
Thr Val Phe Phe Val Leu Met 260 265
270 Met Leu Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val
Gly Asn 275 280 285
Arg Asp Phe Val Glu Gly Val Ser Gly Gly Ala Trp Val Asp Leu Val 290
295 300 Leu Glu His Gly Gly
Cys Val Thr Thr Met Ala Gln Gly Lys Pro Thr 305 310
315 320 Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala
Lys Glu Val Ala Leu Leu 325 330
335 Arg Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala
Thr 340 345 350 Arg
Cys Pro Thr Gln Gly Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln 355
360 365 Gln Tyr Ile Cys Arg Arg
Asp Val Val Asp Arg Gly Trp Gly Asn Gly 370 375
380 Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr
Cys Ala Lys Phe Ser 385 390 395
400 Cys Ser Gly Lys Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu
405 410 415 Tyr Thr
Val Val Val Thr Val His Asn Gly Asp Thr His Ala Val Gly 420
425 430 Asn Asp Thr Ser Asn His Gly
Val Thr Ala Thr Ile Thr Pro Arg Ser 435 440
445 Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu
Leu Thr Leu Asp 450 455 460
Cys Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys 465
470 475 480 Met Lys Lys
Lys Thr Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu 485
490 495 Pro Leu Pro Trp Thr Ala Gly Ala
Asp Thr Ser Glu Val His Trp Asn 500 505
510 Tyr Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala
Lys Arg Gln 515 520 525
Asp Val Thr Val Leu Gly Ser Gln Glu Gly Ala Met His Ser Ala Leu 530
535 540 Ala Gly Ala Thr
Glu Val Asp Ser Gly Asp Gly Asn His Met Phe Ala 545 550
555 560 Gly His Leu Lys Cys Lys Val Arg Met
Glu Lys Leu Arg Ile Lys Gly 565 570
575 Met Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys
Glu Met 580 585 590
Ala Glu Thr Gln His Gly Thr Thr Val Val Lys Val Lys Tyr Glu Gly
595 600 605 Ala Gly Ala Pro
Cys Lys Val Pro Ile Glu Ile Arg Asp Val Asn Lys 610
615 620 Glu Lys Val Val Gly Arg Ile Ile
Ser Ser Thr Pro Leu Ala Glu Asn 625 630
635 640 Thr Asn Ser Val Thr Asn Ile Glu Leu Glu Pro Pro
Phe Gly Asp Ser 645 650
655 Tyr Ile Val Ile Gly Val Gly Asn Ser Ala Leu Thr Leu His Trp Phe
660 665 670 Arg Lys Gly
Ser Ser Ile Gly Lys Met Phe Glu Ser Thr Tyr Arg Gly 675
680 685 Ala Lys Arg Met Ala Ile Leu Gly
Glu Thr Ala Trp Asp Phe Gly Ser 690 695
700 Val Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala Val His
Gln Val Phe 705 710 715
720 Gly Ser Val Tyr Thr Thr Leu Phe Gly Gly Val Ser Trp Met Ile Arg
725 730 735 Ile Leu Ile Gly
Phe Leu Val Leu Trp Ile Gly Thr Asn Ser Arg Asn 740
745 750 Thr Ser Met Ala Met Thr Cys Ile Ala
Ala Gly Ile Val Thr Leu Tyr 755 760
765 Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser
Trp Lys 770 775 780
Asn Lys Glu Leu Lys Cys Gly Ser Gly Ile Phe Ile Thr Asp Asn Val 785
790 795 800 His Thr Trp Thr Glu
Gln Tyr Lys Phe Gln Pro Glu Ser Pro Ser Lys 805
810 815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu
Glu Asp Ile Cys Gly Ile 820 825
830 Arg Ser Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr
Pro 835 840 845 Glu
Leu Asn His Ile Leu Ser Glu Asn Glu Val Lys Leu Thr Ile Met 850
855 860 Thr Gly Asp Ile Lys Gly
Ile Met Gln Ala Gly Lys Arg Ser Leu Arg 865 870
875 880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys
Thr Trp Gly Lys Ala 885 890
895 Lys Met Leu Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly
900 905 910 Pro Glu
Thr Ala Glu Cys Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu 915
920 925 Glu Val Glu Asp Tyr Gly Phe
Gly Val Phe Thr Thr Asn Ile Trp Leu 930 935
940 Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser
Lys Leu Met Ser 945 950 955
960 Ala Ala Ile Lys Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp
965 970 975 Ile Glu Ser
Ala Leu Asn Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe 980
985 990 Ile Glu Val Lys Asn Cys His Trp
Pro Lys Ser His Thr Leu Trp Ser 995 1000
1005 Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro
Lys Asn Leu Ala 1010 1015 1020
Gly Pro Val Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln
1025 1030 1035 Ile Thr Gly
Pro Trp His Leu Gly Lys Leu Glu Met Asp Phe Asp 1040
1045 1050 Phe Cys Asp Gly Thr Thr Val Val
Val Thr Glu Asp Cys Gly Asn 1055 1060
1065 Arg Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys
Leu Ile 1070 1075 1080
Thr Glu Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr 1085
1090 1095 Arg Gly Glu Asp Gly
Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu 1100 1105
1110 Lys Glu Lys Glu Glu Asn Leu Val Asn Ser
Leu Val Thr Ala Gly 1115 1120 1125
His Gly Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala
1130 1135 1140 Leu Phe
Leu Glu Glu Met Leu Arg Thr Arg Val Gly Thr Lys His 1145
1150 1155 Ala Ile Leu Leu Val Ala Val
Ser Phe Val Thr Leu Ile Thr Gly 1160 1165
1170 Asn Met Ser Phe Arg Asp Leu Gly Arg Val Met Val
Met Val Gly 1175 1180 1185
Ala Thr Met Thr Gly Asp Ile Gly Met Gly Val Thr Tyr Leu Ala 1190
1195 1200 Leu Leu Ala Ala Phe
Lys Val Arg Pro Thr Phe Ala Ala Gly Leu 1205 1210
1215 Leu Leu Arg Lys Leu Thr Ser Arg Glu Leu
Met Met Thr Thr Ile 1220 1225 1230
Gly Ile Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu
1235 1240 1245 Glu Leu
Thr Asp Ala Leu Ala Leu Gly Met Met Val Leu Lys Met 1250
1255 1260 Val Arg Asn Met Glu Lys Tyr
Gln Leu Ala Val Thr Ile Met Ala 1265 1270
1275 Ile Leu Cys Val Pro Asn Ala Val Ile Leu Gln Asn
Ala Trp Lys 1280 1285 1290
Val Ser Cys Thr Ile Leu Ala Val Val Ser Val Ser Pro Leu Phe 1295
1300 1305 Leu Thr Ser Ser Gln
Gln Lys Thr Asp Trp Ile Pro Leu Ala Leu 1310 1315
1320 Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile
Phe Leu Thr Thr Leu 1325 1330 1335
Ser Arg Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile
1340 1345 1350 Met Ala
Val Gly Met Val Ser Ile Leu Ala Ser Ser Leu Leu Lys 1355
1360 1365 Asn Asp Ile Pro Met Thr Gly
Pro Leu Val Ala Gly Gly Leu Leu 1370 1375
1380 Thr Val Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp
Leu Glu Leu 1385 1390 1395
Glu Arg Ala Ala Asp Val Lys Trp Glu Asp Gln Ala Glu Ile Ser 1400
1405 1410 Gly Ser Ser Pro Ile
Leu Ser Ile Thr Ile Ser Glu Asp Gly Ser 1415 1420
1425 Met Ser Ile Lys Asn Glu Glu Glu Glu Gln
Thr Leu Thr Ile Leu 1430 1435 1440
Ile Arg Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser
1445 1450 1455 Ile Pro
Ile Thr Ala Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys 1460
1465 1470 Gln Arg Ala Gly Val Leu Trp
Asp Val Pro Ser Pro Pro Pro Met 1475 1480
1485 Gly Lys Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile
Lys Gln Lys 1490 1495 1500
Gly Ile Leu Gly Tyr Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu 1505
1510 1515 Gly Thr Phe His Thr
Met Trp His Val Thr Arg Gly Ala Val Leu 1520 1525
1530 Met His Lys Gly Lys Arg Ile Glu Pro Ser
Trp Ala Asp Val Lys 1535 1540 1545
Lys Asp Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu
1550 1555 1560 Trp Lys
Glu Gly Glu Glu Val Gln Val Leu Ala Leu Glu Pro Gly 1565
1570 1575 Lys Asn Pro Arg Ala Val Gln
Thr Lys Pro Gly Leu Phe Lys Thr 1580 1585
1590 Asn Ala Gly Thr Ile Gly Ala Val Ser Leu Asp Phe
Ser Pro Gly 1595 1600 1605
Thr Ser Gly Ser Pro Ile Ile Asp Lys Lys Gly Lys Val Val Gly 1610
1615 1620 Leu Tyr Gly Asn Gly
Val Val Thr Arg Ser Gly Ala Tyr Val Ser 1625 1630
1635 Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu
Asp Asn Pro Glu Ile 1640 1645 1650
Glu Asp Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu
1655 1660 1665 His Pro
Gly Ala Gly Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val 1670
1675 1680 Arg Glu Ala Ile Lys Arg Gly
Leu Arg Thr Leu Ile Leu Ala Pro 1685 1690
1695 Thr Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu
Arg Gly Leu 1700 1705 1710
Pro Ile Arg Tyr Gln Thr Pro Ala Ile Arg Ala Val His Thr Gly 1715
1720 1725 Arg Glu Ile Val Asp
Leu Met Cys His Ala Thr Phe Thr Met Arg 1730 1735
1740 Leu Leu Ser Pro Val Arg Val Pro Asn Tyr
Asn Leu Ile Ile Met 1745 1750 1755
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1760 1765 1770 Tyr Ile
Ser Thr Arg Val Glu Met Gly Glu Ala Ala Gly Ile Phe 1775
1780 1785 Met Thr Ala Thr Pro Pro Gly
Ser Arg Asp Pro Phe Pro Gln Ser 1790 1795
1800 Asn Ala Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro
Glu Arg Ser 1805 1810 1815
Trp Asn Ser Gly His Glu Trp Val Thr Asp Phe Lys Gly Lys Thr 1820
1825 1830 Val Trp Phe Val Pro
Ser Ile Lys Ala Gly Asn Asp Ile Ala Ala 1835 1840
1845 Cys Leu Arg Lys Asn Gly Lys Lys Val Ile
Gln Leu Ser Arg Lys 1850 1855 1860
Thr Phe Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp
1865 1870 1875 Phe Val
Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys 1880
1885 1890 Ala Glu Arg Val Ile Asp Pro
Arg Arg Cys Met Lys Pro Val Ile 1895 1900
1905 Leu Thr Asp Gly Glu Glu Arg Val Ile Leu Ala Gly
Pro Met Pro 1910 1915 1920
Val Thr His Ser Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg 1925
1930 1935 Asn Pro Lys Asn Glu
Asn Asp Gln Tyr Ile Tyr Met Gly Glu Pro 1940 1945
1950 Leu Glu Asn Asp Glu Asp Cys Ala His Trp
Lys Glu Ala Lys Met 1955 1960 1965
Leu Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met
1970 1975 1980 Phe Glu
Pro Glu Arg Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr 1985
1990 1995 Arg Leu Arg Gly Glu Ala Arg
Lys Thr Phe Val Asp Leu Met Arg 2000 2005
2010 Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Arg Val
Ala Ala Glu 2015 2020 2025
Gly Ile Asn Tyr Ala Asp Arg Arg Trp Cys Phe Asp Gly Val Lys 2030
2035 2040 Asn Asn Gln Ile Leu
Glu Glu Asn Val Glu Val Glu Ile Trp Thr 2045 2050
2055 Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro
Arg Trp Leu Asp Ala 2060 2065 2070
Arg Ile Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe
2075 2080 2085 Ala Ala
Gly Arg Lys Ser Leu Thr Leu Asn Leu Ile Thr Glu Met 2090
2095 2100 Gly Arg Leu Pro Thr Phe Met
Thr Gln Lys Val Arg Asp Ala Leu 2105 2110
2115 Asp Asn Leu Ala Val Leu His Thr Ala Glu Ala Gly
Gly Arg Ala 2120 2125 2130
Tyr Asn His Ala Leu Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu 2135
2140 2145 Leu Leu Leu Thr Leu
Leu Ala Thr Val Thr Gly Gly Ile Phe Leu 2150 2155
2160 Phe Leu Met Ser Ala Arg Gly Ile Gly Lys
Met Thr Leu Gly Met 2165 2170 2175
Cys Cys Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile
2180 2185 2190 Gln Pro
His Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu 2195
2200 2205 Ile Val Leu Leu Ile Pro Glu
Pro Glu Lys Gln Arg Thr Pro Gln 2210 2215
2220 Asp Asn Gln Leu Thr Tyr Val Val Ile Ala Ile Leu
Thr Val Val 2225 2230 2235
Ala Ala Thr Met Ala Asn Glu Met Gly Phe Leu Glu Lys Thr Lys 2240
2245 2250 Lys Asp Leu Gly Leu
Gly Ser Ile Ala Thr Gln Gln Pro Glu Ser 2255 2260
2265 Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala
Ser Ala Trp Thr Leu 2270 2275 2280
Tyr Ala Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser
2285 2290 2295 Ile Glu
Asn Ser Ser Val Asn Val Ser Leu Thr Ala Ile Ala Asn 2300
2305 2310 Gln Ala Thr Val Leu Met Gly
Leu Gly Lys Gly Trp Pro Leu Ser 2315 2320
2325 Lys Met Asp Ile Gly Val Pro Leu Leu Ala Ile Gly
Cys Tyr Ser 2330 2335 2340
Gln Val Asn Pro Ile Thr Leu Thr Ala Ala Leu Phe Leu Leu Val 2345
2350 2355 Ala His Tyr Ala Ile
Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr 2360 2365
2370 Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly
Ile Met Lys Asn Pro 2375 2380 2385
Thr Val Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr
2390 2395 2400 Asp Pro
Lys Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val 2405
2410 2415 Leu Cys Val Thr Gln Val Leu
Met Met Arg Thr Thr Trp Ala Leu 2420 2425
2430 Cys Glu Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser
Thr Leu Trp 2435 2440 2445
Glu Gly Asn Pro Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser 2450
2455 2460 Met Ala Asn Ile Phe
Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu 2465 2470
2475 Leu Phe Ser Ile Met Lys Asn Thr Thr Asn
Thr Arg Arg Gly Thr 2480 2485 2490
Gly Asn Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu
2495 2500 2505 Asn Ala
Leu Gly Lys Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly 2510
2515 2520 Ile Gln Glu Val Asp Arg Thr
Leu Ala Lys Glu Gly Ile Lys Arg 2525 2530
2535 Gly Glu Thr Asp His His Ala Val Ser Arg Gly Ser
Ala Lys Leu 2540 2545 2550
Arg Trp Phe Val Glu Arg Asn Met Val Thr Pro Glu Gly Lys Val 2555
2560 2565 Val Asp Leu Gly Cys
Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Gly 2570 2575
2580 Gly Leu Lys Asn Val Arg Glu Val Lys Gly
Leu Thr Lys Gly Gly 2585 2590 2595
Pro Gly His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn
2600 2605 2610 Leu Val
Arg Leu Gln Ser Gly Val Asp Val Phe Phe Ile Pro Pro 2615
2620 2625 Glu Lys Cys Asp Thr Leu Leu
Cys Asp Ile Gly Glu Ser Ser Pro 2630 2635
2640 Asn Pro Thr Val Glu Ala Gly Arg Thr Leu Arg Val
Leu Asn Leu 2645 2650 2655
Val Glu Asn Trp Leu Asn Asn Asn Thr Gln Phe Cys Ile Lys Val 2660
2665 2670 Leu Asn Pro Tyr Met
Pro Ser Val Ile Glu Lys Met Glu Ala Leu 2675 2680
2685 Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg
Asn Pro Leu Ser Arg 2690 2695 2700
Asn Ser Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn
2705 2710 2715 Ile Val
Ser Ser Val Asn Met Ile Ser Arg Met Leu Ile Asn Arg 2720
2725 2730 Phe Thr Met Arg Tyr Lys Lys
Ala Thr Tyr Glu Pro Asp Val Asp 2735 2740
2745 Leu Gly Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser
Glu Ile Pro 2750 2755 2760
Asn Leu Asp Ile Ile Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu 2765
2770 2775 His Glu Thr Ser Trp
His Tyr Asp Gln Asp His Pro Tyr Lys Thr 2780 2785
2790 Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys
Gln Thr Gly Ser Ala 2795 2800 2805
Ser Ser Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp
2810 2815 2820 Asp Val
Val Pro Met Val Thr Gln Met Ala Met Thr Asp Thr Thr 2825
2830 2835 Pro Phe Gly Gln Gln Arg Val
Phe Lys Glu Lys Val Asp Thr Arg 2840 2845
2850 Thr Gln Glu Pro Lys Glu Gly Thr Lys Lys Leu Met
Lys Ile Thr 2855 2860 2865
Ala Glu Trp Leu Trp Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg 2870
2875 2880 Met Cys Thr Arg Glu
Glu Phe Thr Arg Lys Val Arg Ser Asn Ala 2885 2890
2895 Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn
Lys Trp Lys Ser Ala 2900 2905 2910
Arg Glu Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys
2915 2920 2925 Glu Arg
Asn Leu His Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr 2930
2935 2940 Asn Met Met Gly Lys Arg Glu
Lys Lys Leu Gly Glu Phe Gly Lys 2945 2950
2955 Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu
Gly Ala Arg 2960 2965 2970
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp 2975
2980 2985 Phe Ser Arg Glu Asn
Ser Leu Ser Gly Val Glu Gly Glu Gly Leu 2990 2995
3000 His Lys Leu Gly Tyr Ile Leu Arg Asp Val
Ser Lys Lys Glu Gly 3005 3010 3015
Gly Ala Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3020 3025 3030 Thr Leu
Glu Asp Leu Lys Asn Glu Glu Met Val Thr Asn His Met 3035
3040 3045 Glu Gly Glu His Lys Lys Leu
Ala Glu Ala Ile Phe Lys Leu Thr 3050 3055
3060 Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Thr
Pro Arg Gly 3065 3070 3075
Thr Val Met Asp Ile Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly 3080
3085 3090 Gln Val Gly Thr Tyr
Gly Leu Asn Thr Phe Thr Asn Met Glu Ala 3095 3100
3105 Gln Leu Ile Arg Gln Met Glu Gly Glu Gly
Val Phe Lys Ser Ile 3110 3115 3120
Gln His Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu
3125 3130 3135 Ala Arg
Val Gly Arg Glu Arg Leu Ser Arg Met Ala Ile Ser Gly 3140
3145 3150 Asp Asp Cys Val Val Lys Pro
Leu Asp Asp Arg Phe Ala Ser Ala 3155 3160
3165 Leu Thr Ala Leu Asn Asp Met Gly Lys Ile Arg Lys
Asp Ile Gln 3170 3175 3180
Gln Trp Glu Pro Ser Arg Gly Trp Asn Asp Trp Thr Gln Val Pro 3185
3190 3195 Phe Cys Ser His His
Phe His Glu Leu Ile Met Lys Asp Gly Arg 3200 3205
3210 Val Leu Val Val Pro Cys Arg Asn Gln Asp
Glu Leu Ile Gly Arg 3215 3220 3225
Ala Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala
3230 3235 3240 Cys Leu
Gly Lys Ser Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe 3245
3250 3255 His Arg Arg Asp Leu Arg Leu
Ala Ala Asn Ala Ile Cys Ser Ala 3260 3265
3270 Val Pro Ser His Trp Val Pro Thr Ser Arg Thr Thr
Trp Ser Ile 3275 3280 3285
His Ala Lys His Glu Trp Met Thr Thr Glu Asp Met Leu Thr Val 3290
3295 3300 Trp Asn Arg Val Trp
Ile Gln Glu Asn Pro Trp Met Glu Asp Lys 3305 3310
3315 Thr Pro Val Glu Ser Trp Glu Glu Ile Pro
Tyr Leu Gly Lys Arg 3320 3325 3330
Glu Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala
3335 3340 3345 Thr Trp
Ala Lys Asn Ile Gln Ala Ala Ile Asn Gln Val Arg Ser 3350
3355 3360 Leu Ile Gly Asn Glu Glu Tyr
Thr Asp Tyr Met Pro Ser Met Lys 3365 3370
3375 Arg Phe Arg Arg Glu Glu Glu Glu Ala Gly Val Leu
Trp 3380 3385 3390
2210723DNAArtificial SequenceDerived from Dengue virus serotype 2/Dengue
virus serotype 4, DENV-4e 22agttgttagt ctacgtggac cgacaaagac
agattctttg agggagctaa gctcaatgta 60gttctaacag ttttttaatt agagagcaga
tctctgatga ataaccaacg gaaaaaggcg 120aaaaacacgc ctttcaatat gctgaaacgc
gagagaaacc gcgtgtcgac tgtgcaacag 180ctgacaaaga gattctcact tggaatgctg
cagggacgag gaccattaaa actgttcatg 240gccctggtgg cgttccttcg tttcctaaca
atcccaccaa cagcagggat attgaagaga 300tggggaacaa ttaaaaaatc aaaagctatt
aatgttttga gagggttcag gaaagagatt 360ggaaggatgc tgaacatctt gaataggaga
cgcagctcaa cgataacatt gctgtacttg 420attcccaccg taatggcgtt tcacttgtca
acgcgtgatg gcgaacccct catgatagtg 480gcaaaacatg aaagggggag acctctcttg
tttaagacaa cagaggggat caacaaatgc 540actctcattg ccatggactt gggtgaaatg
tgtgaggaca ctgtcacgta taaatgcccc 600ttactggtca ataccgaacc tgaagacatt
gattgctggt gcaatctcac gtctacctgg 660gtcatgtatg ggacatgcac ccagagcgga
gaacggagac gagagaagcg ctcagtagct 720ttaacaccac attcaggaat gggattggaa
acaagagctg agacatggat gtcatcggaa 780ggggcttgga agcatgctca gagagtagag
agctggatac tcagaaaccc aggattcgcg 840ctcttggcag gatttatggc ttatatgatt
gggcaaacag gaatccagcg aactgtcttc 900tttgtcctaa tgatgctggt cgccccatcc
tacggaatgc gatgcgtagg agtaggaaac 960agagactttg tggaaggagt ctcaggtgga
gcatgggtcg atctggtgct agaacatgga 1020ggatgcgtca caaccatggc ccagggaaaa
ccaaccttgg attttgaact gactaagaca 1080acagccaagg aagtggctct gttaagaacc
tattgcattg aagcctcaat atcaaacata 1140accacggcaa caagatgtcc aacgcaagga
gagccttatc taaaagagga acaagaccaa 1200cagtacattt gccggagaga tgtggtagac
agagggtggg gcaatggctg tggcttgttt 1260ggaaaaggag gagttgtgac atgtgcgaag
ttttcatgtt cggggaagat aacaggcaat 1320ttggtccaaa ttgagaacct tgaatacaca
gtggttgtaa cagtccacaa tggagacacc 1380catgcagtag gaaatgacac gtccaatcat
ggagttacag ccacgataac tcccaggtca 1440ccatcggtgg aagtcaaatt gccggactat
ggagaactaa cactcgattg tgaacccagg 1500tctggaattg actttaatga gatgattctg
atgaaaatga aaaagaaaac atggcttgtg 1560cataagcaat ggtttttgga tctacctcta
ccatggacag caggagcaga cacatcagag 1620gttcactgga attacaaaga gagaatggtg
acatttaagg ttcctcatgc caagagacag 1680gatgtgacag tgctgggatc tcaggaagga
gccatgcatt ctgccctcgc tggagccaca 1740gaagtggact ccggtgatgg aaatcacatg
tttgcaggac atctcaagtg caaagtccgt 1800atggagaaat tgagaatcaa gggaatgtca
tacacgatgt gttcaggaaa gttctcaatt 1860gacaaagaga tggcagaaac acagcatggg
acaacagtgg tgaaagtcaa gtatgaaggt 1920gctggagctc cgtgtaaagt ccccatagag
ataagagatg tgaacaagga aaaagtggtt 1980gggcgtatca tctcatccac ccctttggct
gagaatacca acagtgtaac caacatagag 2040ttagaacccc cctttgggga cagctacata
gtgataggtg ttggaaacag tgcattaaca 2100ctccattggt tcaggaaagg gagttccatt
ggcaagatgt ttgagtccac atacagaggt 2160gcaaaacgaa tggccattct aggtgaaaca
gcttgggatt ttggttccgt tggtggactg 2220ttcacatcat tgggaaaggc tgtgcaccag
gtttttggaa gtgtgtatac aaccctgttt 2280ggaggagtct catggatgat tagaatccta
attgggttcc tagtgttgtg gattggcacg 2340aactcaagga acacttcaat ggctatgacg
tgcatagctg ccggcattgt gacactgtat 2400ttgggagtca tggtgcaggc cgatagtggt
tgcgttgtga gctggaaaaa caaagaactg 2460aaatgtggca gtgggatttt catcacagac
aacgtgcaca catggacaga acaatacaag 2520ttccaaccag aatccccttc aaaactagct
tcagctatcc agaaagccca tgaagaggac 2580atttgtggaa tccgctcagt aacaagactg
gagaatctga tgtggaaaca aataacacca 2640gaattgaatc acattctatc agaaaatgag
gtgaagttaa ctattatgac aggagacatc 2700aaaggaatca tgcaggcagg aaaacgatct
ctgcggcctc agcccactga gctgaagtat 2760tcatggaaaa catggggcaa agcaaaaatg
ctctctacag agtctcataa ccagaccttt 2820ctcattgatg gccccgaaac agcagaatgc
cccaacacaa atagagcttg gaattcgttg 2880gaagttgaag actatggctt tggagtattc
accaccaata tatggctaaa attgaaagaa 2940aaacaggatg tattctgcga ctcaaaactc
atgtcagcgg ccataaaaga caacagagcc 3000gtccatgccg atatgggtta ttggatagaa
agtgcactca atgacacatg gaagatagag 3060aaagcctctt tcattgaagt taaaaactgc
cactggccaa aatcacacac cctctggagc 3120aatggagtgc tagaaagtga gatgataatt
ccaaagaatc tcgctggacc agtgtctcaa 3180cacaactata gaccaggcta ccatacacaa
ataacaggac catggcatct aggtaagctt 3240gagatggact ttgatttctg tgatggaaca
acagtggtag tgactgagga ctgcggaaat 3300agaggaccct ctttgagaac aaccactgcc
tctggaaaac tcataacaga atggtgctgc 3360cgatcttgca cattaccacc gctaagatac
agaggtgagg atgggtgctg gtacgggatg 3420gaaatcagac cattgaagga gaaagaagag
aatttggtca actccttggt cacagctgga 3480catgggcagg tcgacaactt ttcactagga
gtcttgggaa tggcattgtt cctggaggaa 3540atgcttagga cccgagtagg aacgaaacat
gcaatactac tagttgcagt ttcttttgtg 3600acattgatca cagggaacat gtcctttaga
gacctgggaa gagtgatggt tatggtaggc 3660gccactatga cggatgacat aggtatgggc
gtgacttatc ttgccctact agcagccttc 3720aaagtcagac caacttttgc agctggacta
ctcttgagaa agctgacctc caaggaattg 3780atgatgacta ctataggaat tgtactcctc
tcccagagca ccataccaga gaccattctt 3840gagttgactg atgcgttagc cttaggcatg
atggtcctca aaatggtgag aaatatggaa 3900aagtatcaat tggcagtgac tatcatggct
atcttgtgcg tcccaaacgc agtgatatta 3960caaaacgcat ggaaagtgag ttgcacaata
ttggcagtgg tgtccgtttc cccactgttc 4020ttaacatcct cacagcaaaa aacagattgg
ataccattag cattgacgat caaaggtctc 4080aatccaacag ctatttttct aacaaccctc
tcaagaacca gcaagaaaag gagctggcca 4140ttaaatgagg ctatcatggc agtcgggatg
gtgagcattt tagccagttc tctcctaaaa 4200aatgatattc ccatgacagg accattagtg
gctggagggc tcctcactgt gtgctacgtg 4260ctcactggac gatcggccga tttggaactg
gagagagcag ccgatgtcaa atgggaagac 4320caggcagaga tatcaggaag cagtccaatc
ctgtcaataa caatatcaga agatggtagc 4380atgtcgataa aaaatgaaga ggaagaacaa
acactgacca tactcattag aacaggattg 4440ctggtgatct caggactttt tcctgtatca
ataccaatca cggcagcagc atggtacctg 4500tgggaagtga agaaacaacg ggccggagta
ttgtgggatg ttccttcacc cccacccatg 4560ggaaaggctg aactggaaga tggagcctat
agaattaagc aaaaagggat tcttggatat 4620tcccagatcg gagccggagt ttacaaagaa
ggaacattcc atacaatgtg gcatgtcaca 4680cgtggcgctg ttctaatgca taaaggaaag
aggattgaac catcatgggc ggacgtcaag 4740aaagacctaa tatcatatgg aggaggctgg
aagttagaag gagaatggaa ggaaggagaa 4800gaagtccagg tattggcact ggagcctgga
aaaaatccaa gagccgtcca aacgaaacct 4860ggtcttttca aaaccaacgc cggaacaata
ggtgctgtat ctctggactt ttctcctgga 4920acgtcaggat ctccaattat cgacaaaaaa
ggaaaagttg tgggtcttta tggtaatggt 4980gttgttacaa ggagtggagc atatgtgagt
gctatagccc agactgaaaa aagcattgaa 5040gacaacccag agatcgaaga tgacattttc
cgaaagagaa gactgaccat catggacctc 5100cacccaggag cgggaaagac gaagagatac
cttccggcca tagtcagaga agctataaaa 5160cggggtttga gaacattaat cttggccccc
actagagttg tggcagctga aatggaggaa 5220gcccttagag gacttccaat aagataccag
accccagcca tcagagctgt gcacaccggg 5280cgggagattg tggacctaat gtgtcatgcc
acatttacca tgaggctgct atcaccagtt 5340agagtgccaa actacaacct gattatcatg
gacgaagccc atttcacaga cccagcaagt 5400atagcagcta gaggatacat ctcaactcga
gtggagatgg gtgaggcagc tgggattttt 5460atgacagcca ctcccccggg aagcagagac
ccatttcctc agagcaatgc accaatcata 5520gatgaagaaa gagaaatccc tgaacgctcg
tggaattccg gacatgaatg ggtcacggat 5580tttaaaggga agactgtttg gttcgttcca
agtataaaag caggaaatga tatagcagct 5640tgcctgagga aaaatggaaa gaaagtgata
caactcagta ggaagacctt tgattctgag 5700tatgtcaaga ctagaaccaa tgattgggac
ttcgtggtta caactgacat ttcagaaatg 5760ggtgccaatt tcaaggctga gagggttata
gaccccagac gctgcatgaa accagtcata 5820ctaacagatg gtgaagagcg ggtgattctg
gcaggaccta tgccagtgac ccactctagt 5880gcagcacaaa gaagagggag aataggaaga
aatccaaaaa atgagaatga ccagtacata 5940tacatggggg aacctctgga aaatgatgaa
gactgtgcac actggaaaga agctaaaatg 6000ctcctagata acatcaacac gccagaagga
atcattccta gcatgttcga accagagcgt 6060gaaaaggtgg atgccattga tggcgaatac
cgcttgagag gagaagcaag gaaaaccttt 6120gtagacttaa tgagaagagg agacctacca
gtctggttgg cctacagagt ggcagctgaa 6180ggcatcaact acgcagacag aaggtggtgt
tttgatggag tcaagaacaa ccaaatccta 6240gaagaaaacg tggaagttga aatctggaca
aaagaagggg aaaggaagaa attgaaaccc 6300agatggttgg atgctaggat ctattctgac
ccactggcgc taaaagaatt taaggaattt 6360gcagccggaa gaaagtctct gaccctgaac
ctaatcacag aaatgggtag gctcccaacc 6420ttcatgactc agaaggcaag agacgcactg
gacaacttag cagtgctgca cacggctgag 6480gcaggtggaa gggcgtacaa ccatgctctc
agtgaactgc cggagaccct ggagacattg 6540cttttactga cacttctggc tacagtcacg
ggagggatct ttttattctt gatgagcgca 6600aggggcatag ggaagatgac cctgggaatg
tgctgcataa tcacggctag catcctccta 6660tggtacgcac aaatacagcc acactggata
gcagcttcaa taatactgga gttttttctc 6720atagttttgc ttattccaga acctgaaaaa
cagagaacac cccaagacaa ccaactgacc 6780tacgttgtca tagccatcct cacagtggtg
gccgcaacca tggcaaacga gatgggtttc 6840ctagaaaaaa cgaagaaaga tctcggattg
ggaagcattg caacccagca acccgagagc 6900aacatcctgg acatagatct acgtcctgca
tcagcatgga cgctgtatgc cgtggccaca 6960acatttgtta caccaatgtt gagacatagc
attgaaaatt cctcagtgaa tgtgtcccta 7020acagctatag ccaaccaagc cacagtgtta
atgggtctcg ggaaaggatg gccattgtca 7080aagatggaca tcggagttcc ccttctcgcc
attggatgct actcacaagt caaccccata 7140actctcacag cagctctttt cttattggta
gcacattatg ccatcatagg gccaggactc 7200caagcaaaag caaccagaga agctcagaaa
agagcagcgg cgggcatcat gaaaaaccca 7260actgtcgatg gaataacagt gattgaccta
gatccaatac cttatgatcc aaagtttgaa 7320aagcagttgg gacaagtaat gctcctagtc
ctctgcgtga ctcaagtatt gatgatgagg 7380actacatggg ctctgtgtga ggctttaacc
ttagctaccg ggcccatctc cacattgtgg 7440gaaggaaatc cagggaggtt ttggaacact
accattgcgg tgtcaatggc taacattttt 7500agagggagtt acttggccgg agctggactt
ctcttttcta ttatgaagaa cacaaccaac 7560acaagaaggg gaactggcaa cataggagag
acgcttggag agaaatggaa aagccgattg 7620aacgcattgg gaaaaagtga attccagatc
tacaagaaaa gtggaatcca ggaagtggat 7680agaaccttag caaaagaagg cattaaaaga
ggagaaacgg accatcacgc tgtgtcgcga 7740ggctcagcaa aactgagatg gttcgttgag
agaaacatgg tcacaccaga agggaaagta 7800gtggacctcg gttgtggcag aggaggctgg
tcatactatt gtggaggact aaagaatgta 7860agagaagtca aaggcctaac aaaaggagga
ccaggacacg aagaacccat ccccatgtca 7920acatatgggt ggaatctagt gcgtcttcaa
agtggagttg acgttttctt catcccgcca 7980gaaaagtgtg acacattatt gtgtgacata
ggggagtcat caccaaatcc cacagtggaa 8040gcaggacgaa cactcagagt ccttaactta
gtagaaaatt ggttgaacaa caacactcaa 8100ttttgcataa aggttctcaa cccatatatg
ccctcagtca tagaaaaaat ggaagcacta 8160caaaggaaat atggaggagc cttagtgagg
aatccactct cacgaaactc cacacatgag 8220atgtactggg tatccaatgc ttccgggaac
atagtgtcat cagtgaacat gatttcaagg 8280atgttgatca acagatttac aatgagatac
aagaaagcca cttacgagcc ggatgttgac 8340ctcggaagcg gaacccgtaa catcgggatt
gaaagtgaga taccaaacct agatataatt 8400gggaaaagaa tagaaaaaat aaagcaagag
catgaaacat catggcacta tgaccaagac 8460cacccataca aaacgtgggc ataccatggt
agctatgaaa caaaacagac tggatcagca 8520tcatccatgg tcaacggagt ggtcaggctg
ctgacaaaac cttgggacgt cgtccccatg 8580gtgacacaga tggcaatgac agacacgact
ccatttggac aacagcgcgt ttttaaagag 8640aaagtggaca cgagaaccca agaaccgaaa
gaaggcacga agaaactaat gaaaataaca 8700gcagagtggc tttggaaaga attagggaag
aaaaagacac ccaggatgtg caccagagaa 8760gaattcacaa gaaaggtgag aagcaatgca
gccttggggg ccatattcac tgatgagaac 8820aagtggaagt cggcacgtga ggctgttgaa
gatagtaggt tttgggagct ggttgacaag 8880gaaaggaatc tccatcttga aggaaagtgt
gaaacatgtg tgtacaacat gatgggaaaa 8940agagagaaga agctagggga attcggcaag
gcaaaaggca gcagagccat atggtacatg 9000tggcttggag cacgcttctt agagtttgaa
gccctaggat tcttaaatga agatcactgg 9060ttctccagag agaactccct gagtggagtg
gaaggagaag ggctgcacaa gctaggttac 9120attctaagag acgtgagcaa gaaagaggga
ggagcaatgt atgccgatga caccgcagga 9180tgggatacaa gaatcacact agaagaccta
aaaaatgaag aaatggtaac aaaccacatg 9240gaaggagaac acaagaaact agccgaggcc
attttcaaac taacgtacca aaacaaggtg 9300gtgcgtgtgc aaagaccaac accaagaggc
acagtaatgg acatcatatc gagaagagac 9360caaagaggta gtggacaagt tggcacctat
ggactcaata ctttcaccaa tatggaagcc 9420caactaatca gacagatgga gggagaagga
gtctttaaaa gcattcagca cctaacaatc 9480acagaagaaa tcgctgtgca aaactggtta
gcaagagtgg ggcgcgaaag gttatcaaga 9540atggccatca gtggagatga ttgtgttgtg
aaacctttag atgacaggtt cgcaagcgct 9600ttaacagctc taaatgacat gggaaagatt
aggaaagaca tacaacaatg ggaaccttca 9660agaggatgga atgattggac acaagtgccc
ttctgttcac accatttcca tgagttaatc 9720atgaaagacg gtcgcgtact cgttgttcca
tgtagaaacc aagatgaact gattggcaga 9780gcccgaatct cccaaggagc agggtggtct
ttgcgggaga cggcctgttt ggggaagtct 9840tacgcccaaa tgtggagctt gatgtacttc
cacagacgcg acctcaggct ggcggcaaat 9900gctatttgct cggcagtacc atcacattgg
gttccaacaa gtcgaacaac ctggtccata 9960catgctaaac atgaatggat gacaacggaa
gacatgctga cagtctggaa cagggtgtgg 10020attcaagaaa acccatggat ggaagacaaa
actccagtgg aatcatggga ggaaatccca 10080tacttgggga aaagagaaga ccaatggtgc
ggctcattga ttgggttaac aagcagggcc 10140acctgggcaa agaacatcca agcagcaata
aatcaagtta gatcccttat aggcaatgaa 10200gaatacacag attacatgcc atccatgaaa
agattcagaa gagaagagga agaagcagga 10260gttctgtggt agaaagcaaa actaacatga
aacaaggcta gaagtcaggt cggattaagc 10320catagtacgg aaaaaactat gctacctgtg
agccccgtcc aaggacgtta aaagaagtca 10380ggccatcata aatgccatag cttgagtaaa
ctatgcagcc tgtagctcca cctgagaagg 10440tgtaaaaaat ccgggaggcc acaaaccatg
gaagctgtac gcatggcgta gtggactagc 10500ggttagagga gacccctccc ttacaaatcg
cagcaacaat gggggcccaa ggcgagatga 10560agctgtagtc tcgctggaag gactagaggt
tagaggagac ccccccgaaa caaaaaacag 10620catattgacg ctgggaaaga ccagagatcc
tgctgtctcc tcagcatcat tccaggcaca 10680gaacgccaga aaatggaatg gtgctgttga
atcaacaggt tct 10723233391PRTArtificial
SequenceDerived from Dengue virus serotype 2/Dengue virus serotype
4, DEN-4e 23Met Asn Asn Gln Arg Lys Lys Ala Lys Asn Thr Pro Phe Asn Met
Leu 1 5 10 15 Lys
Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu Thr Lys Arg
20 25 30 Phe Ser Leu Gly Met
Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met 35
40 45 Ala Leu Val Ala Phe Leu Arg Phe Leu
Thr Ile Pro Pro Thr Ala Gly 50 55
60 Ile Leu Lys Arg Trp Gly Thr Ile Lys Lys Ser Lys Ala
Ile Asn Val 65 70 75
80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu Asn Ile Leu Asn
85 90 95 Arg Arg Arg Ser
Ser Thr Ile Thr Leu Leu Tyr Leu Ile Pro Thr Val 100
105 110 Met Ala Phe His Leu Ser Thr Arg Asp
Gly Glu Pro Leu Met Ile Val 115 120
125 Ala Lys His Glu Arg Gly Arg Pro Leu Leu Phe Lys Thr Thr
Glu Gly 130 135 140
Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Met Cys Glu 145
150 155 160 Asp Thr Val Thr Tyr
Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu 165
170 175 Asp Ile Asp Cys Trp Cys Asn Leu Thr Ser
Thr Trp Val Met Tyr Gly 180 185
190 Thr Cys Thr Gln Ser Gly Glu Arg Arg Arg Glu Lys Arg Ser Val
Ala 195 200 205 Leu
Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala Glu Thr Trp 210
215 220 Met Ser Ser Glu Gly Ala
Trp Lys His Ala Gln Arg Val Glu Ser Trp 225 230
235 240 Ile Leu Arg Asn Pro Gly Phe Ala Leu Leu Ala
Gly Phe Met Ala Tyr 245 250
255 Met Ile Gly Gln Thr Gly Ile Gln Arg Thr Val Phe Phe Val Leu Met
260 265 270 Met Leu
Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val Gly Asn 275
280 285 Arg Asp Phe Val Glu Gly Val
Ser Gly Gly Ala Trp Val Asp Leu Val 290 295
300 Leu Glu His Gly Gly Cys Val Thr Thr Met Ala Gln
Gly Lys Pro Thr 305 310 315
320 Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala Lys Glu Val Ala Leu Leu
325 330 335 Arg Thr Tyr
Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala Thr 340
345 350 Arg Cys Pro Thr Gln Gly Glu Pro
Tyr Leu Lys Glu Glu Gln Asp Gln 355 360
365 Gln Tyr Ile Cys Arg Arg Asp Val Val Asp Arg Gly Trp
Gly Asn Gly 370 375 380
Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr Cys Ala Lys Phe Ser 385
390 395 400 Cys Ser Gly Lys
Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu 405
410 415 Tyr Thr Val Val Val Thr Val His Asn
Gly Asp Thr His Ala Val Gly 420 425
430 Asn Asp Thr Ser Asn His Gly Val Thr Ala Thr Ile Thr Pro
Arg Ser 435 440 445
Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu Leu Thr Leu Asp 450
455 460 Cys Glu Pro Arg Ser
Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys 465 470
475 480 Met Lys Lys Lys Thr Trp Leu Val His Lys
Gln Trp Phe Leu Asp Leu 485 490
495 Pro Leu Pro Trp Thr Ala Gly Ala Asp Thr Ser Glu Val His Trp
Asn 500 505 510 Tyr
Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala Lys Arg Gln 515
520 525 Asp Val Thr Val Leu Gly
Ser Gln Glu Gly Ala Met His Ser Ala Leu 530 535
540 Ala Gly Ala Thr Glu Val Asp Ser Gly Asp Gly
Asn His Met Phe Ala 545 550 555
560 Gly His Leu Lys Cys Lys Val Arg Met Glu Lys Leu Arg Ile Lys Gly
565 570 575 Met Ser
Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys Glu Met 580
585 590 Ala Glu Thr Gln His Gly Thr
Thr Val Val Lys Val Lys Tyr Glu Gly 595 600
605 Ala Gly Ala Pro Cys Lys Val Pro Ile Glu Ile Arg
Asp Val Asn Lys 610 615 620
Glu Lys Val Val Gly Arg Ile Ile Ser Ser Thr Pro Leu Ala Glu Asn 625
630 635 640 Thr Asn Ser
Val Thr Asn Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser 645
650 655 Tyr Ile Val Ile Gly Val Gly Asn
Ser Ala Leu Thr Leu His Trp Phe 660 665
670 Arg Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ser Thr
Tyr Arg Gly 675 680 685
Ala Lys Arg Met Ala Ile Leu Gly Glu Thr Ala Trp Asp Phe Gly Ser 690
695 700 Val Gly Gly Leu
Phe Thr Ser Leu Gly Lys Ala Val His Gln Val Phe 705 710
715 720 Gly Ser Val Tyr Thr Thr Leu Phe Gly
Gly Val Ser Trp Met Ile Arg 725 730
735 Ile Leu Ile Gly Phe Leu Val Leu Trp Ile Gly Thr Asn Ser
Arg Asn 740 745 750
Thr Ser Met Ala Met Thr Cys Ile Ala Ala Gly Ile Val Thr Leu Tyr
755 760 765 Leu Gly Val Met
Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys 770
775 780 Asn Lys Glu Leu Lys Cys Gly Ser
Gly Ile Phe Ile Thr Asp Asn Val 785 790
795 800 His Thr Trp Thr Glu Gln Tyr Lys Phe Gln Pro Glu
Ser Pro Ser Lys 805 810
815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu Glu Asp Ile Cys Gly Ile
820 825 830 Arg Ser Val
Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro 835
840 845 Glu Leu Asn His Ile Leu Ser Glu
Asn Glu Val Lys Leu Thr Ile Met 850 855
860 Thr Gly Asp Ile Lys Gly Ile Met Gln Ala Gly Lys Arg
Ser Leu Arg 865 870 875
880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala
885 890 895 Lys Met Leu Ser
Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly 900
905 910 Pro Glu Thr Ala Glu Cys Pro Asn Thr
Asn Arg Ala Trp Asn Ser Leu 915 920
925 Glu Val Glu Asp Tyr Gly Phe Gly Val Phe Thr Thr Asn Ile
Trp Leu 930 935 940
Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys Leu Met Ser 945
950 955 960 Ala Ala Ile Lys Asp
Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp 965
970 975 Ile Glu Ser Ala Leu Asn Asp Thr Trp Lys
Ile Glu Lys Ala Ser Phe 980 985
990 Ile Glu Val Lys Asn Cys His Trp Pro Lys Ser His Thr Leu
Trp Ser 995 1000 1005
Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro Lys Asn Leu Ala 1010
1015 1020 Gly Pro Val Ser Gln
His Asn Tyr Arg Pro Gly Tyr His Thr Gln 1025 1030
1035 Ile Thr Gly Pro Trp His Leu Gly Lys Leu
Glu Met Asp Phe Asp 1040 1045 1050
Phe Cys Asp Gly Thr Thr Val Val Val Thr Glu Asp Cys Gly Asn
1055 1060 1065 Arg Gly
Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile 1070
1075 1080 Thr Glu Trp Cys Cys Arg Ser
Cys Thr Leu Pro Pro Leu Arg Tyr 1085 1090
1095 Arg Gly Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile
Arg Pro Leu 1100 1105 1110
Lys Glu Lys Glu Glu Asn Leu Val Asn Ser Leu Val Thr Ala Gly 1115
1120 1125 His Gly Gln Val Asp
Asn Phe Ser Leu Gly Val Leu Gly Met Ala 1130 1135
1140 Leu Phe Leu Glu Glu Met Leu Arg Thr Arg
Val Gly Thr Lys His 1145 1150 1155
Ala Ile Leu Leu Val Ala Val Ser Phe Val Thr Leu Ile Thr Gly
1160 1165 1170 Asn Met
Ser Phe Arg Asp Leu Gly Arg Val Met Val Met Val Gly 1175
1180 1185 Ala Thr Met Thr Asp Asp Ile
Gly Met Gly Val Thr Tyr Leu Ala 1190 1195
1200 Leu Leu Ala Ala Phe Lys Val Arg Pro Thr Phe Ala
Ala Gly Leu 1205 1210 1215
Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu Met Met Thr Thr Ile 1220
1225 1230 Gly Ile Val Leu Leu
Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu 1235 1240
1245 Glu Leu Thr Asp Ala Leu Ala Leu Gly Met
Met Val Leu Lys Met 1250 1255 1260
Val Arg Asn Met Glu Lys Tyr Gln Leu Ala Val Thr Ile Met Ala
1265 1270 1275 Ile Leu
Cys Val Pro Asn Ala Val Ile Leu Gln Asn Ala Trp Lys 1280
1285 1290 Val Ser Cys Thr Ile Leu Ala
Val Val Ser Val Ser Pro Leu Phe 1295 1300
1305 Leu Thr Ser Ser Gln Gln Lys Thr Asp Trp Ile Pro
Leu Ala Leu 1310 1315 1320
Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile Phe Leu Thr Thr Leu 1325
1330 1335 Ser Arg Thr Ser Lys
Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile 1340 1345
1350 Met Ala Val Gly Met Val Ser Ile Leu Ala
Ser Ser Leu Leu Lys 1355 1360 1365
Asn Asp Ile Pro Met Thr Gly Pro Leu Val Ala Gly Gly Leu Leu
1370 1375 1380 Thr Val
Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp Leu Glu Leu 1385
1390 1395 Glu Arg Ala Ala Asp Val Lys
Trp Glu Asp Gln Ala Glu Ile Ser 1400 1405
1410 Gly Ser Ser Pro Ile Leu Ser Ile Thr Ile Ser Glu
Asp Gly Ser 1415 1420 1425
Met Ser Ile Lys Asn Glu Glu Glu Glu Gln Thr Leu Thr Ile Leu 1430
1435 1440 Ile Arg Thr Gly Leu
Leu Val Ile Ser Gly Leu Phe Pro Val Ser 1445 1450
1455 Ile Pro Ile Thr Ala Ala Ala Trp Tyr Leu
Trp Glu Val Lys Lys 1460 1465 1470
Gln Arg Ala Gly Val Leu Trp Asp Val Pro Ser Pro Pro Pro Met
1475 1480 1485 Gly Lys
Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile Lys Gln Lys 1490
1495 1500 Gly Ile Leu Gly Tyr Ser Gln
Ile Gly Ala Gly Val Tyr Lys Glu 1505 1510
1515 Gly Thr Phe His Thr Met Trp His Val Thr Arg Gly
Ala Val Leu 1520 1525 1530
Met His Lys Gly Lys Arg Ile Glu Pro Ser Trp Ala Asp Val Lys 1535
1540 1545 Lys Asp Leu Ile Ser
Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu 1550 1555
1560 Trp Lys Glu Gly Glu Glu Val Gln Val Leu
Ala Leu Glu Pro Gly 1565 1570 1575
Lys Asn Pro Arg Ala Val Gln Thr Lys Pro Gly Leu Phe Lys Thr
1580 1585 1590 Asn Ala
Gly Thr Ile Gly Ala Val Ser Leu Asp Phe Ser Pro Gly 1595
1600 1605 Thr Ser Gly Ser Pro Ile Ile
Asp Lys Lys Gly Lys Val Val Gly 1610 1615
1620 Leu Tyr Gly Asn Gly Val Val Thr Arg Ser Gly Ala
Tyr Val Ser 1625 1630 1635
Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu Asp Asn Pro Glu Ile 1640
1645 1650 Glu Asp Asp Ile Phe
Arg Lys Arg Arg Leu Thr Ile Met Asp Leu 1655 1660
1665 His Pro Gly Ala Gly Lys Thr Lys Arg Tyr
Leu Pro Ala Ile Val 1670 1675 1680
Arg Glu Ala Ile Lys Arg Gly Leu Arg Thr Leu Ile Leu Ala Pro
1685 1690 1695 Thr Arg
Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly Leu 1700
1705 1710 Pro Ile Arg Tyr Gln Thr Pro
Ala Ile Arg Ala Val His Thr Gly 1715 1720
1725 Arg Glu Ile Val Asp Leu Met Cys His Ala Thr Phe
Thr Met Arg 1730 1735 1740
Leu Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Leu Ile Ile Met 1745
1750 1755 Asp Glu Ala His Phe
Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly 1760 1765
1770 Tyr Ile Ser Thr Arg Val Glu Met Gly Glu
Ala Ala Gly Ile Phe 1775 1780 1785
Met Thr Ala Thr Pro Pro Gly Ser Arg Asp Pro Phe Pro Gln Ser
1790 1795 1800 Asn Ala
Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro Glu Arg Ser 1805
1810 1815 Trp Asn Ser Gly His Glu Trp
Val Thr Asp Phe Lys Gly Lys Thr 1820 1825
1830 Val Trp Phe Val Pro Ser Ile Lys Ala Gly Asn Asp
Ile Ala Ala 1835 1840 1845
Cys Leu Arg Lys Asn Gly Lys Lys Val Ile Gln Leu Ser Arg Lys 1850
1855 1860 Thr Phe Asp Ser Glu
Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp 1865 1870
1875 Phe Val Val Thr Thr Asp Ile Ser Glu Met
Gly Ala Asn Phe Lys 1880 1885 1890
Ala Glu Arg Val Ile Asp Pro Arg Arg Cys Met Lys Pro Val Ile
1895 1900 1905 Leu Thr
Asp Gly Glu Glu Arg Val Ile Leu Ala Gly Pro Met Pro 1910
1915 1920 Val Thr His Ser Ser Ala Ala
Gln Arg Arg Gly Arg Ile Gly Arg 1925 1930
1935 Asn Pro Lys Asn Glu Asn Asp Gln Tyr Ile Tyr Met
Gly Glu Pro 1940 1945 1950
Leu Glu Asn Asp Glu Asp Cys Ala His Trp Lys Glu Ala Lys Met 1955
1960 1965 Leu Leu Asp Asn Ile
Asn Thr Pro Glu Gly Ile Ile Pro Ser Met 1970 1975
1980 Phe Glu Pro Glu Arg Glu Lys Val Asp Ala
Ile Asp Gly Glu Tyr 1985 1990 1995
Arg Leu Arg Gly Glu Ala Arg Lys Thr Phe Val Asp Leu Met Arg
2000 2005 2010 Arg Gly
Asp Leu Pro Val Trp Leu Ala Tyr Arg Val Ala Ala Glu 2015
2020 2025 Gly Ile Asn Tyr Ala Asp Arg
Arg Trp Cys Phe Asp Gly Val Lys 2030 2035
2040 Asn Asn Gln Ile Leu Glu Glu Asn Val Glu Val Glu
Ile Trp Thr 2045 2050 2055
Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro Arg Trp Leu Asp Ala 2060
2065 2070 Arg Ile Tyr Ser Asp
Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe 2075 2080
2085 Ala Ala Gly Arg Lys Ser Leu Thr Leu Asn
Leu Ile Thr Glu Met 2090 2095 2100
Gly Arg Leu Pro Thr Phe Met Thr Gln Lys Ala Arg Asp Ala Leu
2105 2110 2115 Asp Asn
Leu Ala Val Leu His Thr Ala Glu Ala Gly Gly Arg Ala 2120
2125 2130 Tyr Asn His Ala Leu Ser Glu
Leu Pro Glu Thr Leu Glu Thr Leu 2135 2140
2145 Leu Leu Leu Thr Leu Leu Ala Thr Val Thr Gly Gly
Ile Phe Leu 2150 2155 2160
Phe Leu Met Ser Ala Arg Gly Ile Gly Lys Met Thr Leu Gly Met 2165
2170 2175 Cys Cys Ile Ile Thr
Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile 2180 2185
2190 Gln Pro His Trp Ile Ala Ala Ser Ile Ile
Leu Glu Phe Phe Leu 2195 2200 2205
Ile Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln
2210 2215 2220 Asp Asn
Gln Leu Thr Tyr Val Val Ile Ala Ile Leu Thr Val Val 2225
2230 2235 Ala Ala Thr Met Ala Asn Glu
Met Gly Phe Leu Glu Lys Thr Lys 2240 2245
2250 Lys Asp Leu Gly Leu Gly Ser Ile Ala Thr Gln Gln
Pro Glu Ser 2255 2260 2265
Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu 2270
2275 2280 Tyr Ala Val Ala Thr
Thr Phe Val Thr Pro Met Leu Arg His Ser 2285 2290
2295 Ile Glu Asn Ser Ser Val Asn Val Ser Leu
Thr Ala Ile Ala Asn 2300 2305 2310
Gln Ala Thr Val Leu Met Gly Leu Gly Lys Gly Trp Pro Leu Ser
2315 2320 2325 Lys Met
Asp Ile Gly Val Pro Leu Leu Ala Ile Gly Cys Tyr Ser 2330
2335 2340 Gln Val Asn Pro Ile Thr Leu
Thr Ala Ala Leu Phe Leu Leu Val 2345 2350
2355 Ala His Tyr Ala Ile Ile Gly Pro Gly Leu Gln Ala
Lys Ala Thr 2360 2365 2370
Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly Ile Met Lys Asn Pro 2375
2380 2385 Thr Val Asp Gly Ile
Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr 2390 2395
2400 Asp Pro Lys Phe Glu Lys Gln Leu Gly Gln
Val Met Leu Leu Val 2405 2410 2415
Leu Cys Val Thr Gln Val Leu Met Met Arg Thr Thr Trp Ala Leu
2420 2425 2430 Cys Glu
Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser Thr Leu Trp 2435
2440 2445 Glu Gly Asn Pro Gly Arg Phe
Trp Asn Thr Thr Ile Ala Val Ser 2450 2455
2460 Met Ala Asn Ile Phe Arg Gly Ser Tyr Leu Ala Gly
Ala Gly Leu 2465 2470 2475
Leu Phe Ser Ile Met Lys Asn Thr Thr Asn Thr Arg Arg Gly Thr 2480
2485 2490 Gly Asn Ile Gly Glu
Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu 2495 2500
2505 Asn Ala Leu Gly Lys Ser Glu Phe Gln Ile
Tyr Lys Lys Ser Gly 2510 2515 2520
Ile Gln Glu Val Asp Arg Thr Leu Ala Lys Glu Gly Ile Lys Arg
2525 2530 2535 Gly Glu
Thr Asp His His Ala Val Ser Arg Gly Ser Ala Lys Leu 2540
2545 2550 Arg Trp Phe Val Glu Arg Asn
Met Val Thr Pro Glu Gly Lys Val 2555 2560
2565 Val Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr
Tyr Cys Gly 2570 2575 2580
Gly Leu Lys Asn Val Arg Glu Val Lys Gly Leu Thr Lys Gly Gly 2585
2590 2595 Pro Gly His Glu Glu
Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn 2600 2605
2610 Leu Val Arg Leu Gln Ser Gly Val Asp Val
Phe Phe Ile Pro Pro 2615 2620 2625
Glu Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro
2630 2635 2640 Asn Pro
Thr Val Glu Ala Gly Arg Thr Leu Arg Val Leu Asn Leu 2645
2650 2655 Val Glu Asn Trp Leu Asn Asn
Asn Thr Gln Phe Cys Ile Lys Val 2660 2665
2670 Leu Asn Pro Tyr Met Pro Ser Val Ile Glu Lys Met
Glu Ala Leu 2675 2680 2685
Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg Asn Pro Leu Ser Arg 2690
2695 2700 Asn Ser Thr His Glu
Met Tyr Trp Val Ser Asn Ala Ser Gly Asn 2705 2710
2715 Ile Val Ser Ser Val Asn Met Ile Ser Arg
Met Leu Ile Asn Arg 2720 2725 2730
Phe Thr Met Arg Tyr Lys Lys Ala Thr Tyr Glu Pro Asp Val Asp
2735 2740 2745 Leu Gly
Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser Glu Ile Pro 2750
2755 2760 Asn Leu Asp Ile Ile Gly Lys
Arg Ile Glu Lys Ile Lys Gln Glu 2765 2770
2775 His Glu Thr Ser Trp His Tyr Asp Gln Asp His Pro
Tyr Lys Thr 2780 2785 2790
Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys Gln Thr Gly Ser Ala 2795
2800 2805 Ser Ser Met Val Asn
Gly Val Val Arg Leu Leu Thr Lys Pro Trp 2810 2815
2820 Asp Val Val Pro Met Val Thr Gln Met Ala
Met Thr Asp Thr Thr 2825 2830 2835
Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg
2840 2845 2850 Thr Gln
Glu Pro Lys Glu Gly Thr Lys Lys Leu Met Lys Ile Thr 2855
2860 2865 Ala Glu Trp Leu Trp Lys Glu
Leu Gly Lys Lys Lys Thr Pro Arg 2870 2875
2880 Met Cys Thr Arg Glu Glu Phe Thr Arg Lys Val Arg
Ser Asn Ala 2885 2890 2895
Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn Lys Trp Lys Ser Ala 2900
2905 2910 Arg Glu Ala Val Glu
Asp Ser Arg Phe Trp Glu Leu Val Asp Lys 2915 2920
2925 Glu Arg Asn Leu His Leu Glu Gly Lys Cys
Glu Thr Cys Val Tyr 2930 2935 2940
Asn Met Met Gly Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys
2945 2950 2955 Ala Lys
Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg 2960
2965 2970 Phe Leu Glu Phe Glu Ala Leu
Gly Phe Leu Asn Glu Asp His Trp 2975 2980
2985 Phe Ser Arg Glu Asn Ser Leu Ser Gly Val Glu Gly
Glu Gly Leu 2990 2995 3000
His Lys Leu Gly Tyr Ile Leu Arg Asp Val Ser Lys Lys Glu Gly 3005
3010 3015 Gly Ala Met Tyr Ala
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile 3020 3025
3030 Thr Leu Glu Asp Leu Lys Asn Glu Glu Met
Val Thr Asn His Met 3035 3040 3045
Glu Gly Glu His Lys Lys Leu Ala Glu Ala Ile Phe Lys Leu Thr
3050 3055 3060 Tyr Gln
Asn Lys Val Val Arg Val Gln Arg Pro Thr Pro Arg Gly 3065
3070 3075 Thr Val Met Asp Ile Ile Ser
Arg Arg Asp Gln Arg Gly Ser Gly 3080 3085
3090 Gln Val Gly Thr Tyr Gly Leu Asn Thr Phe Thr Asn
Met Glu Ala 3095 3100 3105
Gln Leu Ile Arg Gln Met Glu Gly Glu Gly Val Phe Lys Ser Ile 3110
3115 3120 Gln His Leu Thr Ile
Thr Glu Glu Ile Ala Val Gln Asn Trp Leu 3125 3130
3135 Ala Arg Val Gly Arg Glu Arg Leu Ser Arg
Met Ala Ile Ser Gly 3140 3145 3150
Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Ser Ala
3155 3160 3165 Leu Thr
Ala Leu Asn Asp Met Gly Lys Ile Arg Lys Asp Ile Gln 3170
3175 3180 Gln Trp Glu Pro Ser Arg Gly
Trp Asn Asp Trp Thr Gln Val Pro 3185 3190
3195 Phe Cys Ser His His Phe His Glu Leu Ile Met Lys
Asp Gly Arg 3200 3205 3210
Val Leu Val Val Pro Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg 3215
3220 3225 Ala Arg Ile Ser Gln
Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala 3230 3235
3240 Cys Leu Gly Lys Ser Tyr Ala Gln Met Trp
Ser Leu Met Tyr Phe 3245 3250 3255
His Arg Arg Asp Leu Arg Leu Ala Ala Asn Ala Ile Cys Ser Ala
3260 3265 3270 Val Pro
Ser His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser Ile 3275
3280 3285 His Ala Lys His Glu Trp Met
Thr Thr Glu Asp Met Leu Thr Val 3290 3295
3300 Trp Asn Arg Val Trp Ile Gln Glu Asn Pro Trp Met
Glu Asp Lys 3305 3310 3315
Thr Pro Val Glu Ser Trp Glu Glu Ile Pro Tyr Leu Gly Lys Arg 3320
3325 3330 Glu Asp Gln Trp Cys
Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala 3335 3340
3345 Thr Trp Ala Lys Asn Ile Gln Ala Ala Ile
Asn Gln Val Arg Ser 3350 3355 3360
Leu Ile Gly Asn Glu Glu Tyr Thr Asp Tyr Met Pro Ser Met Lys
3365 3370 3375 Arg Phe
Arg Arg Glu Glu Glu Glu Ala Gly Val Leu Trp 3380
3385 3390 2410723DNAArtificial SequenceDerived from
Dengue virus serotype 2/Dengue virus serotype 4, DEN, 4h
24agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaatgta
60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg
120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag
180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg
240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga
300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt
360ggaaggatgc tgaacatctt gaataggaga cgcagctctg caggcatgat cattatgctg
420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gcgaacccct catgatagtg
480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat caacaaatgc
540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta taaatgcccc
600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac gtctacctgg
660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg ctcagtagct
720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat gtcatcggaa
780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc aggattcgcg
840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg aactgtcttc
900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg agtaggaaac
960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct agaacatgga
1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact gactaagaca
1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat atcaaacata
1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga acaagaccaa
1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg tggcttgttt
1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat aacaggcaat
1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa tggagacacc
1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac tcccaggtca
1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg tgaacccagg
1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac atggcttgtg
1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga cacatcagag
1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc caagagacag
1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc tggagccaca
1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg caaagtccgt
1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa gttctcaatt
1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa gtatgaaggt
1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga aaaagtggtt
1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac caacatagag
2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag tgcattaaca
2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac atacagaggt
2160gcaaaacgaa tggccattct aggtaaaaca gcttgggatt ttggttccgt tggtggactg
2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac aaccctgttt
2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg gattggcacg
2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt gacactgtat
2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa caaagaactg
2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga acaatacaag
2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca tgaagaggac
2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca aataacacca
2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac aggagacatc
2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga gctgaagtat
2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa ccagaccttt
2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg gaattcgttg
2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa attgaaagaa
2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga caacagagcc
3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg gaagatagag
3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac cctctggagc
3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc agtgtctcaa
3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct aggtaagctt
3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga ctgcggaaat
3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga atggtgctgc
3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg gtacgggatg
3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt cacagctgga
3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt cctggaggaa
3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt ttcttttgtg
3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt tatggtaggc
3660gccactatga cggatgacat aggtatgggc gtgacttatc ttgccctact agcagccttc
3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc caaggaattg
3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga gaccattctt
3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag aaatatggaa
3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc agtgatatta
3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc cccactgttc
4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat caaaggtctc
4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag gagctggcca
4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc tctcctaaaa
4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt gtgctacgtg
4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa atgggaagac
4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga agatggtagc
4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag aacaggattg
4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc atggtacctg
4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc cccacccatg
4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat tcttggatat
4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg gcatgtcaca
4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc ggacgtcaag
4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa ggaaggagaa
4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca aacgaaacct
4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt ttctcctgga
4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta tggtaatggt
4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa aagcattgaa
5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat catggacctc
5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga agctataaaa
5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga aatggaggaa
5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt gcacaccggg
5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct atcaccagtt
5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga cccagcaagt
5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc tgggattttt
5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc accaatcata
5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg ggtcacggat
5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga tatagcagct
5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt tgattctgag
5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat ttcagaaatg
5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa accagtcata
5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac ccactctagt
5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga ccagtacata
5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga agctaaaatg
6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga accagagcgt
6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag gaaaaccttt
6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt ggcagctgaa
6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa ccaaatccta
6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa attgaaaccc
6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt taaggaattt
6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag gctcccaacc
6420ttcatgactc agaaggcaag agacgcactg gacaacttag cagtgctgca cacggctgag
6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct ggagacattg
6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt gatgagcgca
6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag catcctccta
6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga gttttttctc
6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa ccaactgacc
6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga gatgggtttc
6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca acccgagagc
6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc cgtggccaca
6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa tgtgtcccta
7020acagctatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg gccattgtca
7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt caaccccata
7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg gccaggactc
7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat gaaaaaccca
7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc aaagtttgaa
7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt gatgatgagg
7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc cacattgtgg
7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc taacattttt
7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa cacaaccaac
7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa aagccgattg
7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca ggaagtggat
7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc tgtgtcgcga
7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga agggaaagta
7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact aaagaatgta
7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat ccccatgtca
7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt catcccgcca
7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc cacagtggaa
8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa caacactcaa
8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat ggaagcacta
8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc cacacatgag
8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat gatttcaagg
8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc ggatgttgac
8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct agatataatt
8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta tgaccaagac
8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac tggatcagca
8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt cgtccccatg
8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt ttttaaagag
8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat gaaaataaca
8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg caccagagaa
8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac tgatgagaac
8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct ggttgacaag
8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat gatgggaaaa
8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat atggtacatg
9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga agatcactgg
9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa gctaggttac
9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga caccgcagga
9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac aaaccacatg
9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca aaacaaggtg
9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc gagaagagac
9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa tatggaagcc
9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca cctaacaatc
9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag gttatcaaga
9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt cgcaagcgct
9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg ggaaccttca
9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca tgagttaatc
9720atgaaagacg gtcgcgtact cgttgttcca tgtagaaacc aagatgaact gattggcaga
9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt ggggaagtct
9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct ggcggcaaat
9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac ctggtccata
9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa cagggtgtgg
10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga ggaaatccca
10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac aagcagggcc
10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat aggcaatgaa
10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga agaagcagga
10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt cggattaagc
10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta aaagaagtca
10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca cctgagaagg
10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta gtggactagc
10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa ggcgagatga
10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa caaaaaacag
10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat tccaggcaca
10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tct
10723253391PRTArtificial SequenceDerived from Dengue virus serotype
2/Dengue virus serotype 4, DEN4h 25Met Asn Asn Gln Arg Lys Lys Ala
Lys Asn Thr Pro Phe Asn Met Leu 1 5 10
15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu
Thr Lys Arg 20 25 30
Phe Ser Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met
35 40 45 Ala Leu Val Ala
Phe Leu Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly 50
55 60 Ile Leu Lys Arg Trp Gly Thr Ile
Lys Lys Ser Lys Ala Ile Asn Val 65 70
75 80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu
Asn Ile Leu Asn 85 90
95 Arg Arg Arg Ser Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val
100 105 110 Met Ala Phe
His Leu Thr Thr Arg Asp Gly Glu Pro Leu Met Ile Val 115
120 125 Ala Lys His Glu Arg Gly Arg Pro
Leu Leu Phe Lys Thr Thr Glu Gly 130 135
140 Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly Glu
Met Cys Glu 145 150 155
160 Asp Thr Val Thr Tyr Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu
165 170 175 Asp Ile Asp Cys
Trp Cys Asn Leu Thr Ser Thr Trp Val Met Tyr Gly 180
185 190 Thr Cys Thr Gln Ser Gly Glu Arg Arg
Arg Glu Lys Arg Ser Val Ala 195 200
205 Leu Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala Glu
Thr Trp 210 215 220
Met Ser Ser Glu Gly Ala Trp Lys His Ala Gln Arg Val Glu Ser Trp 225
230 235 240 Ile Leu Arg Asn Pro
Gly Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr 245
250 255 Met Ile Gly Gln Thr Gly Ile Gln Arg Thr
Val Phe Phe Val Leu Met 260 265
270 Met Leu Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val Gly
Asn 275 280 285 Arg
Asp Phe Val Glu Gly Val Ser Gly Gly Ala Trp Val Asp Leu Val 290
295 300 Leu Glu His Gly Gly Cys
Val Thr Thr Met Ala Gln Gly Lys Pro Thr 305 310
315 320 Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala Lys
Glu Val Ala Leu Leu 325 330
335 Arg Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala Thr
340 345 350 Arg Cys
Pro Thr Gln Gly Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln 355
360 365 Gln Tyr Ile Cys Arg Arg Asp
Val Val Asp Arg Gly Trp Gly Asn Gly 370 375
380 Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr Cys
Ala Lys Phe Ser 385 390 395
400 Cys Ser Gly Lys Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu
405 410 415 Tyr Thr Val
Val Val Thr Val His Asn Gly Asp Thr His Ala Val Gly 420
425 430 Asn Asp Thr Ser Asn His Gly Val
Thr Ala Thr Ile Thr Pro Arg Ser 435 440
445 Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu Leu
Thr Leu Asp 450 455 460
Cys Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys 465
470 475 480 Met Lys Lys Lys
Thr Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu 485
490 495 Pro Leu Pro Trp Thr Ala Gly Ala Asp
Thr Ser Glu Val His Trp Asn 500 505
510 Tyr Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala Lys
Arg Gln 515 520 525
Asp Val Thr Val Leu Gly Ser Gln Glu Gly Ala Met His Ser Ala Leu 530
535 540 Ala Gly Ala Thr Glu
Val Asp Ser Gly Asp Gly Asn His Met Phe Ala 545 550
555 560 Gly His Leu Lys Cys Lys Val Arg Met Glu
Lys Leu Arg Ile Lys Gly 565 570
575 Met Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys Glu
Met 580 585 590 Ala
Glu Thr Gln His Gly Thr Thr Val Val Lys Val Lys Tyr Glu Gly 595
600 605 Ala Gly Ala Pro Cys Lys
Val Pro Ile Glu Ile Arg Asp Val Asn Lys 610 615
620 Glu Lys Val Val Gly Arg Ile Ile Ser Ser Thr
Pro Leu Ala Glu Asn 625 630 635
640 Thr Asn Ser Val Thr Asn Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser
645 650 655 Tyr Ile
Val Ile Gly Val Gly Asn Ser Ala Leu Thr Leu His Trp Phe 660
665 670 Arg Lys Gly Ser Ser Ile Gly
Lys Met Phe Glu Ser Thr Tyr Arg Gly 675 680
685 Ala Lys Arg Met Ala Ile Leu Gly Lys Thr Ala Trp
Asp Phe Gly Ser 690 695 700
Val Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala Val His Gln Val Phe 705
710 715 720 Gly Ser Val
Tyr Thr Thr Leu Phe Gly Gly Val Ser Trp Met Ile Arg 725
730 735 Ile Leu Ile Gly Phe Leu Val Leu
Trp Ile Gly Thr Asn Ser Arg Asn 740 745
750 Thr Ser Met Ala Met Thr Cys Ile Ala Ala Gly Ile Val
Thr Leu Tyr 755 760 765
Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys 770
775 780 Asn Lys Glu Leu
Lys Cys Gly Ser Gly Ile Phe Ile Thr Asp Asn Val 785 790
795 800 His Thr Trp Thr Glu Gln Tyr Lys Phe
Gln Pro Glu Ser Pro Ser Lys 805 810
815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu Glu Asp Ile Cys
Gly Ile 820 825 830
Arg Ser Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro
835 840 845 Glu Leu Asn His
Ile Leu Ser Glu Asn Glu Val Lys Leu Thr Ile Met 850
855 860 Thr Gly Asp Ile Lys Gly Ile Met
Gln Ala Gly Lys Arg Ser Leu Arg 865 870
875 880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr
Trp Gly Lys Ala 885 890
895 Lys Met Leu Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly
900 905 910 Pro Glu Thr
Ala Glu Cys Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu 915
920 925 Glu Val Glu Asp Tyr Gly Phe Gly
Val Phe Thr Thr Asn Ile Trp Leu 930 935
940 Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys
Leu Met Ser 945 950 955
960 Ala Ala Ile Lys Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp
965 970 975 Ile Glu Ser Ala
Leu Asn Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe 980
985 990 Ile Glu Val Lys Asn Cys His Trp
Pro Lys Ser His Thr Leu Trp Ser 995 1000
1005 Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro
Lys Asn Leu Ala 1010 1015 1020
Gly Pro Val Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln
1025 1030 1035 Ile Thr Gly
Pro Trp His Leu Gly Lys Leu Glu Met Asp Phe Asp 1040
1045 1050 Phe Cys Asp Gly Thr Thr Val Val
Val Thr Glu Asp Cys Gly Asn 1055 1060
1065 Arg Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys
Leu Ile 1070 1075 1080
Thr Glu Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr 1085
1090 1095 Arg Gly Glu Asp Gly
Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu 1100 1105
1110 Lys Glu Lys Glu Glu Asn Leu Val Asn Ser
Leu Val Thr Ala Gly 1115 1120 1125
His Gly Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala
1130 1135 1140 Leu Phe
Leu Glu Glu Met Leu Arg Thr Arg Val Gly Thr Lys His 1145
1150 1155 Ala Ile Leu Leu Val Ala Val
Ser Phe Val Thr Leu Ile Thr Gly 1160 1165
1170 Asn Met Ser Phe Arg Asp Leu Gly Arg Val Met Val
Met Val Gly 1175 1180 1185
Ala Thr Met Thr Asp Asp Ile Gly Met Gly Val Thr Tyr Leu Ala 1190
1195 1200 Leu Leu Ala Ala Phe
Lys Val Arg Pro Thr Phe Ala Ala Gly Leu 1205 1210
1215 Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu
Met Met Thr Thr Ile 1220 1225 1230
Gly Ile Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu
1235 1240 1245 Glu Leu
Thr Asp Ala Leu Ala Leu Gly Met Met Val Leu Lys Met 1250
1255 1260 Val Arg Asn Met Glu Lys Tyr
Gln Leu Ala Val Thr Ile Met Ala 1265 1270
1275 Ile Leu Cys Val Pro Asn Ala Val Ile Leu Gln Asn
Ala Trp Lys 1280 1285 1290
Val Ser Cys Thr Ile Leu Ala Val Val Ser Val Ser Pro Leu Phe 1295
1300 1305 Leu Thr Ser Ser Gln
Gln Lys Thr Asp Trp Ile Pro Leu Ala Leu 1310 1315
1320 Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile
Phe Leu Thr Thr Leu 1325 1330 1335
Ser Arg Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile
1340 1345 1350 Met Ala
Val Gly Met Val Ser Ile Leu Ala Ser Ser Leu Leu Lys 1355
1360 1365 Asn Asp Ile Pro Met Thr Gly
Pro Leu Val Ala Gly Gly Leu Leu 1370 1375
1380 Thr Val Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp
Leu Glu Leu 1385 1390 1395
Glu Arg Ala Ala Asp Val Lys Trp Glu Asp Gln Ala Glu Ile Ser 1400
1405 1410 Gly Ser Ser Pro Ile
Leu Ser Ile Thr Ile Ser Glu Asp Gly Ser 1415 1420
1425 Met Ser Ile Lys Asn Glu Glu Glu Glu Gln
Thr Leu Thr Ile Leu 1430 1435 1440
Ile Arg Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser
1445 1450 1455 Ile Pro
Ile Thr Ala Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys 1460
1465 1470 Gln Arg Ala Gly Val Leu Trp
Asp Val Pro Ser Pro Pro Pro Met 1475 1480
1485 Gly Lys Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile
Lys Gln Lys 1490 1495 1500
Gly Ile Leu Gly Tyr Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu 1505
1510 1515 Gly Thr Phe His Thr
Met Trp His Val Thr Arg Gly Ala Val Leu 1520 1525
1530 Met His Lys Gly Lys Arg Ile Glu Pro Ser
Trp Ala Asp Val Lys 1535 1540 1545
Lys Asp Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu
1550 1555 1560 Trp Lys
Glu Gly Glu Glu Val Gln Val Leu Ala Leu Glu Pro Gly 1565
1570 1575 Lys Asn Pro Arg Ala Val Gln
Thr Lys Pro Gly Leu Phe Lys Thr 1580 1585
1590 Asn Ala Gly Thr Ile Gly Ala Val Ser Leu Asp Phe
Ser Pro Gly 1595 1600 1605
Thr Ser Gly Ser Pro Ile Ile Asp Lys Lys Gly Lys Val Val Gly 1610
1615 1620 Leu Tyr Gly Asn Gly
Val Val Thr Arg Ser Gly Ala Tyr Val Ser 1625 1630
1635 Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu
Asp Asn Pro Glu Ile 1640 1645 1650
Glu Asp Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu
1655 1660 1665 His Pro
Gly Ala Gly Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val 1670
1675 1680 Arg Glu Ala Ile Lys Arg Gly
Leu Arg Thr Leu Ile Leu Ala Pro 1685 1690
1695 Thr Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu
Arg Gly Leu 1700 1705 1710
Pro Ile Arg Tyr Gln Thr Pro Ala Ile Arg Ala Val His Thr Gly 1715
1720 1725 Arg Glu Ile Val Asp
Leu Met Cys His Ala Thr Phe Thr Met Arg 1730 1735
1740 Leu Leu Ser Pro Val Arg Val Pro Asn Tyr
Asn Leu Ile Ile Met 1745 1750 1755
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1760 1765 1770 Tyr Ile
Ser Thr Arg Val Glu Met Gly Glu Ala Ala Gly Ile Phe 1775
1780 1785 Met Thr Ala Thr Pro Pro Gly
Ser Arg Asp Pro Phe Pro Gln Ser 1790 1795
1800 Asn Ala Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro
Glu Arg Ser 1805 1810 1815
Trp Asn Ser Gly His Glu Trp Val Thr Asp Phe Lys Gly Lys Thr 1820
1825 1830 Val Trp Phe Val Pro
Ser Ile Lys Ala Gly Asn Asp Ile Ala Ala 1835 1840
1845 Cys Leu Arg Lys Asn Gly Lys Lys Val Ile
Gln Leu Ser Arg Lys 1850 1855 1860
Thr Phe Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp
1865 1870 1875 Phe Val
Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys 1880
1885 1890 Ala Glu Arg Val Ile Asp Pro
Arg Arg Cys Met Lys Pro Val Ile 1895 1900
1905 Leu Thr Asp Gly Glu Glu Arg Val Ile Leu Ala Gly
Pro Met Pro 1910 1915 1920
Val Thr His Ser Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg 1925
1930 1935 Asn Pro Lys Asn Glu
Asn Asp Gln Tyr Ile Tyr Met Gly Glu Pro 1940 1945
1950 Leu Glu Asn Asp Glu Asp Cys Ala His Trp
Lys Glu Ala Lys Met 1955 1960 1965
Leu Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met
1970 1975 1980 Phe Glu
Pro Glu Arg Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr 1985
1990 1995 Arg Leu Arg Gly Glu Ala Arg
Lys Thr Phe Val Asp Leu Met Arg 2000 2005
2010 Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Arg Val
Ala Ala Glu 2015 2020 2025
Gly Ile Asn Tyr Ala Asp Arg Arg Trp Cys Phe Asp Gly Val Lys 2030
2035 2040 Asn Asn Gln Ile Leu
Glu Glu Asn Val Glu Val Glu Ile Trp Thr 2045 2050
2055 Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro
Arg Trp Leu Asp Ala 2060 2065 2070
Arg Ile Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe
2075 2080 2085 Ala Ala
Gly Arg Lys Ser Leu Thr Leu Asn Leu Ile Thr Glu Met 2090
2095 2100 Gly Arg Leu Pro Thr Phe Met
Thr Gln Lys Ala Arg Asp Ala Leu 2105 2110
2115 Asp Asn Leu Ala Val Leu His Thr Ala Glu Ala Gly
Gly Arg Ala 2120 2125 2130
Tyr Asn His Ala Leu Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu 2135
2140 2145 Leu Leu Leu Thr Leu
Leu Ala Thr Val Thr Gly Gly Ile Phe Leu 2150 2155
2160 Phe Leu Met Ser Ala Arg Gly Ile Gly Lys
Met Thr Leu Gly Met 2165 2170 2175
Cys Cys Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile
2180 2185 2190 Gln Pro
His Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu 2195
2200 2205 Ile Val Leu Leu Ile Pro Glu
Pro Glu Lys Gln Arg Thr Pro Gln 2210 2215
2220 Asp Asn Gln Leu Thr Tyr Val Val Ile Ala Ile Leu
Thr Val Val 2225 2230 2235
Ala Ala Thr Met Ala Asn Glu Met Gly Phe Leu Glu Lys Thr Lys 2240
2245 2250 Lys Asp Leu Gly Leu
Gly Ser Ile Ala Thr Gln Gln Pro Glu Ser 2255 2260
2265 Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala
Ser Ala Trp Thr Leu 2270 2275 2280
Tyr Ala Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser
2285 2290 2295 Ile Glu
Asn Ser Ser Val Asn Val Ser Leu Thr Ala Ile Ala Asn 2300
2305 2310 Gln Ala Thr Val Leu Met Gly
Leu Gly Lys Gly Trp Pro Leu Ser 2315 2320
2325 Lys Met Asp Ile Gly Val Pro Leu Leu Ala Ile Gly
Cys Tyr Ser 2330 2335 2340
Gln Val Asn Pro Ile Thr Leu Thr Ala Ala Leu Phe Leu Leu Val 2345
2350 2355 Ala His Tyr Ala Ile
Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr 2360 2365
2370 Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly
Ile Met Lys Asn Pro 2375 2380 2385
Thr Val Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr
2390 2395 2400 Asp Pro
Lys Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val 2405
2410 2415 Leu Cys Val Thr Gln Val Leu
Met Met Arg Thr Thr Trp Ala Leu 2420 2425
2430 Cys Glu Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser
Thr Leu Trp 2435 2440 2445
Glu Gly Asn Pro Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser 2450
2455 2460 Met Ala Asn Ile Phe
Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu 2465 2470
2475 Leu Phe Ser Ile Met Lys Asn Thr Thr Asn
Thr Arg Arg Gly Thr 2480 2485 2490
Gly Asn Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu
2495 2500 2505 Asn Ala
Leu Gly Lys Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly 2510
2515 2520 Ile Gln Glu Val Asp Arg Thr
Leu Ala Lys Glu Gly Ile Lys Arg 2525 2530
2535 Gly Glu Thr Asp His His Ala Val Ser Arg Gly Ser
Ala Lys Leu 2540 2545 2550
Arg Trp Phe Val Glu Arg Asn Met Val Thr Pro Glu Gly Lys Val 2555
2560 2565 Val Asp Leu Gly Cys
Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Gly 2570 2575
2580 Gly Leu Lys Asn Val Arg Glu Val Lys Gly
Leu Thr Lys Gly Gly 2585 2590 2595
Pro Gly His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn
2600 2605 2610 Leu Val
Arg Leu Gln Ser Gly Val Asp Val Phe Phe Ile Pro Pro 2615
2620 2625 Glu Lys Cys Asp Thr Leu Leu
Cys Asp Ile Gly Glu Ser Ser Pro 2630 2635
2640 Asn Pro Thr Val Glu Ala Gly Arg Thr Leu Arg Val
Leu Asn Leu 2645 2650 2655
Val Glu Asn Trp Leu Asn Asn Asn Thr Gln Phe Cys Ile Lys Val 2660
2665 2670 Leu Asn Pro Tyr Met
Pro Ser Val Ile Glu Lys Met Glu Ala Leu 2675 2680
2685 Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg
Asn Pro Leu Ser Arg 2690 2695 2700
Asn Ser Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn
2705 2710 2715 Ile Val
Ser Ser Val Asn Met Ile Ser Arg Met Leu Ile Asn Arg 2720
2725 2730 Phe Thr Met Arg Tyr Lys Lys
Ala Thr Tyr Glu Pro Asp Val Asp 2735 2740
2745 Leu Gly Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser
Glu Ile Pro 2750 2755 2760
Asn Leu Asp Ile Ile Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu 2765
2770 2775 His Glu Thr Ser Trp
His Tyr Asp Gln Asp His Pro Tyr Lys Thr 2780 2785
2790 Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys
Gln Thr Gly Ser Ala 2795 2800 2805
Ser Ser Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp
2810 2815 2820 Asp Val
Val Pro Met Val Thr Gln Met Ala Met Thr Asp Thr Thr 2825
2830 2835 Pro Phe Gly Gln Gln Arg Val
Phe Lys Glu Lys Val Asp Thr Arg 2840 2845
2850 Thr Gln Glu Pro Lys Glu Gly Thr Lys Lys Leu Met
Lys Ile Thr 2855 2860 2865
Ala Glu Trp Leu Trp Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg 2870
2875 2880 Met Cys Thr Arg Glu
Glu Phe Thr Arg Lys Val Arg Ser Asn Ala 2885 2890
2895 Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn
Lys Trp Lys Ser Ala 2900 2905 2910
Arg Glu Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys
2915 2920 2925 Glu Arg
Asn Leu His Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr 2930
2935 2940 Asn Met Met Gly Lys Arg Glu
Lys Lys Leu Gly Glu Phe Gly Lys 2945 2950
2955 Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu
Gly Ala Arg 2960 2965 2970
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp 2975
2980 2985 Phe Ser Arg Glu Asn
Ser Leu Ser Gly Val Glu Gly Glu Gly Leu 2990 2995
3000 His Lys Leu Gly Tyr Ile Leu Arg Asp Val
Ser Lys Lys Glu Gly 3005 3010 3015
Gly Ala Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3020 3025 3030 Thr Leu
Glu Asp Leu Lys Asn Glu Glu Met Val Thr Asn His Met 3035
3040 3045 Glu Gly Glu His Lys Lys Leu
Ala Glu Ala Ile Phe Lys Leu Thr 3050 3055
3060 Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Thr
Pro Arg Gly 3065 3070 3075
Thr Val Met Asp Ile Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly 3080
3085 3090 Gln Val Gly Thr Tyr
Gly Leu Asn Thr Phe Thr Asn Met Glu Ala 3095 3100
3105 Gln Leu Ile Arg Gln Met Glu Gly Glu Gly
Val Phe Lys Ser Ile 3110 3115 3120
Gln His Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu
3125 3130 3135 Ala Arg
Val Gly Arg Glu Arg Leu Ser Arg Met Ala Ile Ser Gly 3140
3145 3150 Asp Asp Cys Val Val Lys Pro
Leu Asp Asp Arg Phe Ala Ser Ala 3155 3160
3165 Leu Thr Ala Leu Asn Asp Met Gly Lys Ile Arg Lys
Asp Ile Gln 3170 3175 3180
Gln Trp Glu Pro Ser Arg Gly Trp Asn Asp Trp Thr Gln Val Pro 3185
3190 3195 Phe Cys Ser His His
Phe His Glu Leu Ile Met Lys Asp Gly Arg 3200 3205
3210 Val Leu Val Val Pro Cys Arg Asn Gln Asp
Glu Leu Ile Gly Arg 3215 3220 3225
Ala Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala
3230 3235 3240 Cys Leu
Gly Lys Ser Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe 3245
3250 3255 His Arg Arg Asp Leu Arg Leu
Ala Ala Asn Ala Ile Cys Ser Ala 3260 3265
3270 Val Pro Ser His Trp Val Pro Thr Ser Arg Thr Thr
Trp Ser Ile 3275 3280 3285
His Ala Lys His Glu Trp Met Thr Thr Glu Asp Met Leu Thr Val 3290
3295 3300 Trp Asn Arg Val Trp
Ile Gln Glu Asn Pro Trp Met Glu Asp Lys 3305 3310
3315 Thr Pro Val Glu Ser Trp Glu Glu Ile Pro
Tyr Leu Gly Lys Arg 3320 3325 3330
Glu Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala
3335 3340 3345 Thr Trp
Ala Lys Asn Ile Gln Ala Ala Ile Asn Gln Val Arg Ser 3350
3355 3360 Leu Ile Gly Asn Glu Glu Tyr
Thr Asp Tyr Met Pro Ser Met Lys 3365 3370
3375 Arg Phe Arg Arg Glu Glu Glu Glu Ala Gly Val Leu
Trp 3380 3385 3390
265PRTArtificial SequenceDerived from Dengue-2 virus 26Gly Arg Ile Gly
Arg 1 5 275PRTArtificial SequenceDerived from Dengue-2
virus 27Gly Ala Gly Lys Thr 1 5 2810723DNAArtificial
SequenceDerived from Dengue virus serotype 2/Dengue virus serotype
4, DenVax-4g 28agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa
gctcaacgta 60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg
gaaaaaggcg 120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac
tgtgcaacag 180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa
actgttcatg 240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat
attgaagaga 300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag
gaaagagatt 360ggaaggatgc tgaacatctt gaataggaga cgcagctctg caggcatgat
cattatgctg 420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gcgaacccct
catgatagtg 480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat
caacaaatgc 540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta
taaatgcccc 600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac
gtctacctgg 660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg
ctcagtagct 720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat
gtcatcggaa 780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc
aggattcgcg 840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg
aactgtcttc 900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg
agtaggaaac 960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct
agaacatgga 1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact
gactaagaca 1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat
atcaaacata 1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga
acaagaccaa 1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg
tggcttgttt 1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat
aacaggcaat 1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa
tggagacacc 1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac
tcccaggtca 1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg
tgaacccagg 1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac
atggcttgtg 1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga
cacatcagag 1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc
caagagacag 1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc
tggagccaca 1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg
caaagtccgt 1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa
gttctcaatt 1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa
gtatgaaggt 1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga
aaaagtggtt 1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac
caacatagag 2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag
tgcattaaca 2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac
atacagaggt 2160gcaaaacgaa tggccattct aggtgaaaca gcttgggatt ttggttccgt
tggtggactg 2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac
aaccctgttt 2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg
gattggcacg 2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt
gacactgtat 2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa
caaagaactg 2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga
acaatacaag 2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca
tgaagaggac 2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca
aataacacca 2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac
aggagacatc 2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga
gctgaagtat 2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa
ccagaccttt 2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg
gaattcgttg 2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa
attgaaagaa 2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga
caacagagcc 3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg
gaagatagag 3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac
cctctggagc 3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc
agtgtctcaa 3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct
aggtaagctt 3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga
ctgcggaaat 3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga
atggtgctgc 3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg
gtacgggatg 3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt
cacagctgga 3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt
cctggaggaa 3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt
ttcttttgtg 3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt
tatggtaggc 3660gccactatga cggatgacat aggtatgggc gtgacttatc ttgccctact
agcagccttc 3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc
caaggaattg 3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga
gaccattctt 3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag
aaatatggaa 3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc
agtgatatta 3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc
cccactgctc 4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat
caaaggtctc 4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag
gagctggcca 4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc
tctcctaaaa 4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt
gtgctacgtg 4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa
atgggaagac 4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga
agatggtagc 4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag
aacaggattg 4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc
atggtacctg 4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc
cccacccatg 4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat
tcttggatat 4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg
gcatgtcaca 4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc
ggacgtcaag 4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa
ggaaggagaa 4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca
aacgaaacct 4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt
ttctcctgga 4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta
tggtaatggt 4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa
aagcattgaa 5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat
catggacctc 5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga
agctataaaa 5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga
aatggaggaa 5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt
gcacaccggg 5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct
atcaccagtt 5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga
cccagcaagt 5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc
tgggattttt 5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc
accaatcata 5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg
ggtcacggat 5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga
tatagcagct 5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt
tgattctgag 5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat
ttcagaaatg 5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa
accagtcata 5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac
ccactctagt 5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga
ccagtacata 5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga
agctaaaatg 6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga
accagagcgt 6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag
gaaaaccttt 6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt
ggcagctgaa 6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa
ccaaatccta 6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa
attgaaaccc 6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt
taaggaattt 6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag
gctcccaacc 6420ttcatgactc agaaggcaag agacgcactg gacaacttag cagtgctgca
cacggctgag 6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct
ggagacattg 6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt
gatgagcgga 6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag
catcctccta 6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga
gttttttctc 6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa
ccaactgacc 6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga
gatgggtttc 6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca
acccgagagc 6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc
cgtggccaca 6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa
tgtgtcccta 7020acagctatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg
gccattgtca 7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt
caaccccata 7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg
gccaggactc 7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat
gaaaaaccca 7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc
aaagtttgaa 7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt
gatgatgagg 7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc
cacattgtgg 7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc
taacattttt 7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa
cacaaccaac 7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa
aagccgattg 7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca
ggaagtggat 7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc
tgtgtcgcga 7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga
agggaaagta 7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact
aaagaatgta 7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat
ccccatgtca 7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt
catcccgcca 7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc
cacagtggaa 8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa
caacactcaa 8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat
ggaagcacta 8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc
cacacatgag 8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat
gatttcaagg 8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc
ggatgttgac 8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct
agatataatt 8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta
tgaccaagac 8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac
tggatcagca 8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt
cgtccccatg 8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt
ttttaaagag 8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat
gaaaataaca 8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg
caccagagaa 8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac
tgatgagaac 8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct
ggttgacaag 8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat
gatgggaaaa 8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat
atggtacatg 9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga
agatcactgg 9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa
gctaggttac 9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga
caccgcagga 9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac
aaaccacatg 9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca
aaacaaggtg 9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc
gagaagagac 9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa
tatggaagcc 9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca
cctaacaatc 9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag
gttatcaaga 9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt
cgcaagcgct 9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg
ggaaccttca 9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca
tgagttaatc 9720atgaaagacg gtcgcgtact cgttgttcca tgtagaaacc aagatgaact
gattggcaga 9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt
ggggaagtct 9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct
ggcggcaaat 9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac
ctggtccata 9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa
cagggtgtgg 10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga
ggaaatccca 10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac
aagcagggcc 10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat
aggcaatgaa 10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga
agaagcagga 10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt
cggattaagc 10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta
aaagaagtca 10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca
cctgagaagg 10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta
gtggactagc 10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa
ggcgagatga 10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa
caaaaaacag 10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat
tccaggcaca 10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tct
10723293391PRTArtificial SequenceDerived from Dengue virus
serotype 2/Dengue virus serotype 4, DenVax-4g 29Met Asn Asn Gln Arg
Lys Lys Ala Lys Asn Thr Pro Phe Asn Met Leu 1 5
10 15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val
Gln Gln Leu Thr Lys Arg 20 25
30 Phe Ser Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe
Met 35 40 45 Ala
Leu Val Ala Phe Leu Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly 50
55 60 Ile Leu Lys Arg Trp Gly
Thr Ile Lys Lys Ser Lys Ala Ile Asn Val 65 70
75 80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met
Leu Asn Ile Leu Asn 85 90
95 Arg Arg Arg Ser Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val
100 105 110 Met Ala
Phe His Leu Thr Thr Arg Asp Gly Glu Pro Leu Met Ile Val 115
120 125 Ala Lys His Glu Arg Gly Arg
Pro Leu Leu Phe Lys Thr Thr Glu Gly 130 135
140 Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly
Glu Met Cys Glu 145 150 155
160 Asp Thr Val Thr Tyr Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu
165 170 175 Asp Ile Asp
Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Met Tyr Gly 180
185 190 Thr Cys Thr Gln Ser Gly Glu Arg
Arg Arg Glu Lys Arg Ser Val Ala 195 200
205 Leu Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala
Glu Thr Trp 210 215 220
Met Ser Ser Glu Gly Ala Trp Lys His Ala Gln Arg Val Glu Ser Trp 225
230 235 240 Ile Leu Arg Asn
Pro Gly Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr 245
250 255 Met Ile Gly Gln Thr Gly Ile Gln Arg
Thr Val Phe Phe Val Leu Met 260 265
270 Met Leu Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val
Gly Asn 275 280 285
Arg Asp Phe Val Glu Gly Val Ser Gly Gly Ala Trp Val Asp Leu Val 290
295 300 Leu Glu His Gly Gly
Cys Val Thr Thr Met Ala Gln Gly Lys Pro Thr 305 310
315 320 Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala
Lys Glu Val Ala Leu Leu 325 330
335 Arg Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala
Thr 340 345 350 Arg
Cys Pro Thr Gln Gly Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln 355
360 365 Gln Tyr Ile Cys Arg Arg
Asp Val Val Asp Arg Gly Trp Gly Asn Gly 370 375
380 Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr
Cys Ala Lys Phe Ser 385 390 395
400 Cys Ser Gly Lys Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu
405 410 415 Tyr Thr
Val Val Val Thr Val His Asn Gly Asp Thr His Ala Val Gly 420
425 430 Asn Asp Thr Ser Asn His Gly
Val Thr Ala Thr Ile Thr Pro Arg Ser 435 440
445 Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu
Leu Thr Leu Asp 450 455 460
Cys Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys 465
470 475 480 Met Lys Lys
Lys Thr Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu 485
490 495 Pro Leu Pro Trp Thr Ala Gly Ala
Asp Thr Ser Glu Val His Trp Asn 500 505
510 Tyr Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala
Lys Arg Gln 515 520 525
Asp Val Thr Val Leu Gly Ser Gln Glu Gly Ala Met His Ser Ala Leu 530
535 540 Ala Gly Ala Thr
Glu Val Asp Ser Gly Asp Gly Asn His Met Phe Ala 545 550
555 560 Gly His Leu Lys Cys Lys Val Arg Met
Glu Lys Leu Arg Ile Lys Gly 565 570
575 Met Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys
Glu Met 580 585 590
Ala Glu Thr Gln His Gly Thr Thr Val Val Lys Val Lys Tyr Glu Gly
595 600 605 Ala Gly Ala Pro
Cys Lys Val Pro Ile Glu Ile Arg Asp Val Asn Lys 610
615 620 Glu Lys Val Val Gly Arg Ile Ile
Ser Ser Thr Pro Leu Ala Glu Asn 625 630
635 640 Thr Asn Ser Val Thr Asn Ile Glu Leu Glu Pro Pro
Phe Gly Asp Ser 645 650
655 Tyr Ile Val Ile Gly Val Gly Asn Ser Ala Leu Thr Leu His Trp Phe
660 665 670 Arg Lys Gly
Ser Ser Ile Gly Lys Met Phe Glu Ser Thr Tyr Arg Gly 675
680 685 Ala Lys Arg Met Ala Ile Leu Gly
Glu Thr Ala Trp Asp Phe Gly Ser 690 695
700 Val Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala Val His
Gln Val Phe 705 710 715
720 Gly Ser Val Tyr Thr Thr Leu Phe Gly Gly Val Ser Trp Met Ile Arg
725 730 735 Ile Leu Ile Gly
Phe Leu Val Leu Trp Ile Gly Thr Asn Ser Arg Asn 740
745 750 Thr Ser Met Ala Met Thr Cys Ile Ala
Ala Gly Ile Val Thr Leu Tyr 755 760
765 Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser
Trp Lys 770 775 780
Asn Lys Glu Leu Lys Cys Gly Ser Gly Ile Phe Ile Thr Asp Asn Val 785
790 795 800 His Thr Trp Thr Glu
Gln Tyr Lys Phe Gln Pro Glu Ser Pro Ser Lys 805
810 815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu
Glu Asp Ile Cys Gly Ile 820 825
830 Arg Ser Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr
Pro 835 840 845 Glu
Leu Asn His Ile Leu Ser Glu Asn Glu Val Lys Leu Thr Ile Met 850
855 860 Thr Gly Asp Ile Lys Gly
Ile Met Gln Ala Gly Lys Arg Ser Leu Arg 865 870
875 880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys
Thr Trp Gly Lys Ala 885 890
895 Lys Met Leu Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly
900 905 910 Pro Glu
Thr Ala Glu Cys Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu 915
920 925 Glu Val Glu Asp Tyr Gly Phe
Gly Val Phe Thr Thr Asn Ile Trp Leu 930 935
940 Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser
Lys Leu Met Ser 945 950 955
960 Ala Ala Ile Lys Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp
965 970 975 Ile Glu Ser
Ala Leu Asn Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe 980
985 990 Ile Glu Val Lys Asn Cys His Trp
Pro Lys Ser His Thr Leu Trp Ser 995 1000
1005 Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro
Lys Asn Leu Ala 1010 1015 1020
Gly Pro Val Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln
1025 1030 1035 Ile Thr Gly
Pro Trp His Leu Gly Lys Leu Glu Met Asp Phe Asp 1040
1045 1050 Phe Cys Asp Gly Thr Thr Val Val
Val Thr Glu Asp Cys Gly Asn 1055 1060
1065 Arg Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys
Leu Ile 1070 1075 1080
Thr Glu Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr 1085
1090 1095 Arg Gly Glu Asp Gly
Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu 1100 1105
1110 Lys Glu Lys Glu Glu Asn Leu Val Asn Ser
Leu Val Thr Ala Gly 1115 1120 1125
His Gly Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala
1130 1135 1140 Leu Phe
Leu Glu Glu Met Leu Arg Thr Arg Val Gly Thr Lys His 1145
1150 1155 Ala Ile Leu Leu Val Ala Val
Ser Phe Val Thr Leu Ile Thr Gly 1160 1165
1170 Asn Met Ser Phe Arg Asp Leu Gly Arg Val Met Val
Met Val Gly 1175 1180 1185
Ala Thr Met Thr Asp Asp Ile Gly Met Gly Val Thr Tyr Leu Ala 1190
1195 1200 Leu Leu Ala Ala Phe
Lys Val Arg Pro Thr Phe Ala Ala Gly Leu 1205 1210
1215 Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu
Met Met Thr Thr Ile 1220 1225 1230
Gly Ile Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu
1235 1240 1245 Glu Leu
Thr Asp Ala Leu Ala Leu Gly Met Met Val Leu Lys Met 1250
1255 1260 Val Arg Asn Met Glu Lys Tyr
Gln Leu Ala Val Thr Ile Met Ala 1265 1270
1275 Ile Leu Cys Val Pro Asn Ala Val Ile Leu Gln Asn
Ala Trp Lys 1280 1285 1290
Val Ser Cys Thr Ile Leu Ala Val Val Ser Val Ser Pro Leu Leu 1295
1300 1305 Leu Thr Ser Ser Gln
Gln Lys Thr Asp Trp Ile Pro Leu Ala Leu 1310 1315
1320 Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile
Phe Leu Thr Thr Leu 1325 1330 1335
Ser Arg Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile
1340 1345 1350 Met Ala
Val Gly Met Val Ser Ile Leu Ala Ser Ser Leu Leu Lys 1355
1360 1365 Asn Asp Ile Pro Met Thr Gly
Pro Leu Val Ala Gly Gly Leu Leu 1370 1375
1380 Thr Val Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp
Leu Glu Leu 1385 1390 1395
Glu Arg Ala Ala Asp Val Lys Trp Glu Asp Gln Ala Glu Ile Ser 1400
1405 1410 Gly Ser Ser Pro Ile
Leu Ser Ile Thr Ile Ser Glu Asp Gly Ser 1415 1420
1425 Met Ser Ile Lys Asn Glu Glu Glu Glu Gln
Thr Leu Thr Ile Leu 1430 1435 1440
Ile Arg Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser
1445 1450 1455 Ile Pro
Ile Thr Ala Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys 1460
1465 1470 Gln Arg Ala Gly Val Leu Trp
Asp Val Pro Ser Pro Pro Pro Met 1475 1480
1485 Gly Lys Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile
Lys Gln Lys 1490 1495 1500
Gly Ile Leu Gly Tyr Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu 1505
1510 1515 Gly Thr Phe His Thr
Met Trp His Val Thr Arg Gly Ala Val Leu 1520 1525
1530 Met His Lys Gly Lys Arg Ile Glu Pro Ser
Trp Ala Asp Val Lys 1535 1540 1545
Lys Asp Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu
1550 1555 1560 Trp Lys
Glu Gly Glu Glu Val Gln Val Leu Ala Leu Glu Pro Gly 1565
1570 1575 Lys Asn Pro Arg Ala Val Gln
Thr Lys Pro Gly Leu Phe Lys Thr 1580 1585
1590 Asn Ala Gly Thr Ile Gly Ala Val Ser Leu Asp Phe
Ser Pro Gly 1595 1600 1605
Thr Ser Gly Ser Pro Ile Ile Asp Lys Lys Gly Lys Val Val Gly 1610
1615 1620 Leu Tyr Gly Asn Gly
Val Val Thr Arg Ser Gly Ala Tyr Val Ser 1625 1630
1635 Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu
Asp Asn Pro Glu Ile 1640 1645 1650
Glu Asp Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu
1655 1660 1665 His Pro
Gly Ala Gly Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val 1670
1675 1680 Arg Glu Ala Ile Lys Arg Gly
Leu Arg Thr Leu Ile Leu Ala Pro 1685 1690
1695 Thr Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu
Arg Gly Leu 1700 1705 1710
Pro Ile Arg Tyr Gln Thr Pro Ala Ile Arg Ala Val His Thr Gly 1715
1720 1725 Arg Glu Ile Val Asp
Leu Met Cys His Ala Thr Phe Thr Met Arg 1730 1735
1740 Leu Leu Ser Pro Val Arg Val Pro Asn Tyr
Asn Leu Ile Ile Met 1745 1750 1755
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1760 1765 1770 Tyr Ile
Ser Thr Arg Val Glu Met Gly Glu Ala Ala Gly Ile Phe 1775
1780 1785 Met Thr Ala Thr Pro Pro Gly
Ser Arg Asp Pro Phe Pro Gln Ser 1790 1795
1800 Asn Ala Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro
Glu Arg Ser 1805 1810 1815
Trp Asn Ser Gly His Glu Trp Val Thr Asp Phe Lys Gly Lys Thr 1820
1825 1830 Val Trp Phe Val Pro
Ser Ile Lys Ala Gly Asn Asp Ile Ala Ala 1835 1840
1845 Cys Leu Arg Lys Asn Gly Lys Lys Val Ile
Gln Leu Ser Arg Lys 1850 1855 1860
Thr Phe Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp
1865 1870 1875 Phe Val
Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys 1880
1885 1890 Ala Glu Arg Val Ile Asp Pro
Arg Arg Cys Met Lys Pro Val Ile 1895 1900
1905 Leu Thr Asp Gly Glu Glu Arg Val Ile Leu Ala Gly
Pro Met Pro 1910 1915 1920
Val Thr His Ser Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg 1925
1930 1935 Asn Pro Lys Asn Glu
Asn Asp Gln Tyr Ile Tyr Met Gly Glu Pro 1940 1945
1950 Leu Glu Asn Asp Glu Asp Cys Ala His Trp
Lys Glu Ala Lys Met 1955 1960 1965
Leu Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met
1970 1975 1980 Phe Glu
Pro Glu Arg Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr 1985
1990 1995 Arg Leu Arg Gly Glu Ala Arg
Lys Thr Phe Val Asp Leu Met Arg 2000 2005
2010 Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Arg Val
Ala Ala Glu 2015 2020 2025
Gly Ile Asn Tyr Ala Asp Arg Arg Trp Cys Phe Asp Gly Val Lys 2030
2035 2040 Asn Asn Gln Ile Leu
Glu Glu Asn Val Glu Val Glu Ile Trp Thr 2045 2050
2055 Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro
Arg Trp Leu Asp Ala 2060 2065 2070
Arg Ile Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe
2075 2080 2085 Ala Ala
Gly Arg Lys Ser Leu Thr Leu Asn Leu Ile Thr Glu Met 2090
2095 2100 Gly Arg Leu Pro Thr Phe Met
Thr Gln Lys Ala Arg Asp Ala Leu 2105 2110
2115 Asp Asn Leu Ala Val Leu His Thr Ala Glu Ala Gly
Gly Arg Ala 2120 2125 2130
Tyr Asn His Ala Leu Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu 2135
2140 2145 Leu Leu Leu Thr Leu
Leu Ala Thr Val Thr Gly Gly Ile Phe Leu 2150 2155
2160 Phe Leu Met Ser Gly Arg Gly Ile Gly Lys
Met Thr Leu Gly Met 2165 2170 2175
Cys Cys Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile
2180 2185 2190 Gln Pro
His Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu 2195
2200 2205 Ile Val Leu Leu Ile Pro Glu
Pro Glu Lys Gln Arg Thr Pro Gln 2210 2215
2220 Asp Asn Gln Leu Thr Tyr Val Val Ile Ala Ile Leu
Thr Val Val 2225 2230 2235
Ala Ala Thr Met Ala Asn Glu Met Gly Phe Leu Glu Lys Thr Lys 2240
2245 2250 Lys Asp Leu Gly Leu
Gly Ser Ile Ala Thr Gln Gln Pro Glu Ser 2255 2260
2265 Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala
Ser Ala Trp Thr Leu 2270 2275 2280
Tyr Ala Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser
2285 2290 2295 Ile Glu
Asn Ser Ser Val Asn Val Ser Leu Thr Ala Ile Ala Asn 2300
2305 2310 Gln Ala Thr Val Leu Met Gly
Leu Gly Lys Gly Trp Pro Leu Ser 2315 2320
2325 Lys Met Asp Ile Gly Val Pro Leu Leu Ala Ile Gly
Cys Tyr Ser 2330 2335 2340
Gln Val Asn Pro Ile Thr Leu Thr Ala Ala Leu Phe Leu Leu Val 2345
2350 2355 Ala His Tyr Ala Ile
Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr 2360 2365
2370 Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly
Ile Met Lys Asn Pro 2375 2380 2385
Thr Val Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr
2390 2395 2400 Asp Pro
Lys Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val 2405
2410 2415 Leu Cys Val Thr Gln Val Leu
Met Met Arg Thr Thr Trp Ala Leu 2420 2425
2430 Cys Glu Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser
Thr Leu Trp 2435 2440 2445
Glu Gly Asn Pro Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser 2450
2455 2460 Met Ala Asn Ile Phe
Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu 2465 2470
2475 Leu Phe Ser Ile Met Lys Asn Thr Thr Asn
Thr Arg Arg Gly Thr 2480 2485 2490
Gly Asn Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu
2495 2500 2505 Asn Ala
Leu Gly Lys Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly 2510
2515 2520 Ile Gln Glu Val Asp Arg Thr
Leu Ala Lys Glu Gly Ile Lys Arg 2525 2530
2535 Gly Glu Thr Asp His His Ala Val Ser Arg Gly Ser
Ala Lys Leu 2540 2545 2550
Arg Trp Phe Val Glu Arg Asn Met Val Thr Pro Glu Gly Lys Val 2555
2560 2565 Val Asp Leu Gly Cys
Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Gly 2570 2575
2580 Gly Leu Lys Asn Val Arg Glu Val Lys Gly
Leu Thr Lys Gly Gly 2585 2590 2595
Pro Gly His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn
2600 2605 2610 Leu Val
Arg Leu Gln Ser Gly Val Asp Val Phe Phe Ile Pro Pro 2615
2620 2625 Glu Lys Cys Asp Thr Leu Leu
Cys Asp Ile Gly Glu Ser Ser Pro 2630 2635
2640 Asn Pro Thr Val Glu Ala Gly Arg Thr Leu Arg Val
Leu Asn Leu 2645 2650 2655
Val Glu Asn Trp Leu Asn Asn Asn Thr Gln Phe Cys Ile Lys Val 2660
2665 2670 Leu Asn Pro Tyr Met
Pro Ser Val Ile Glu Lys Met Glu Ala Leu 2675 2680
2685 Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg
Asn Pro Leu Ser Arg 2690 2695 2700
Asn Ser Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn
2705 2710 2715 Ile Val
Ser Ser Val Asn Met Ile Ser Arg Met Leu Ile Asn Arg 2720
2725 2730 Phe Thr Met Arg Tyr Lys Lys
Ala Thr Tyr Glu Pro Asp Val Asp 2735 2740
2745 Leu Gly Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser
Glu Ile Pro 2750 2755 2760
Asn Leu Asp Ile Ile Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu 2765
2770 2775 His Glu Thr Ser Trp
His Tyr Asp Gln Asp His Pro Tyr Lys Thr 2780 2785
2790 Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys
Gln Thr Gly Ser Ala 2795 2800 2805
Ser Ser Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp
2810 2815 2820 Asp Val
Val Pro Met Val Thr Gln Met Ala Met Thr Asp Thr Thr 2825
2830 2835 Pro Phe Gly Gln Gln Arg Val
Phe Lys Glu Lys Val Asp Thr Arg 2840 2845
2850 Thr Gln Glu Pro Lys Glu Gly Thr Lys Lys Leu Met
Lys Ile Thr 2855 2860 2865
Ala Glu Trp Leu Trp Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg 2870
2875 2880 Met Cys Thr Arg Glu
Glu Phe Thr Arg Lys Val Arg Ser Asn Ala 2885 2890
2895 Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn
Lys Trp Lys Ser Ala 2900 2905 2910
Arg Glu Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys
2915 2920 2925 Glu Arg
Asn Leu His Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr 2930
2935 2940 Asn Met Met Gly Lys Arg Glu
Lys Lys Leu Gly Glu Phe Gly Lys 2945 2950
2955 Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu
Gly Ala Arg 2960 2965 2970
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp 2975
2980 2985 Phe Ser Arg Glu Asn
Ser Leu Ser Gly Val Glu Gly Glu Gly Leu 2990 2995
3000 His Lys Leu Gly Tyr Ile Leu Arg Asp Val
Ser Lys Lys Glu Gly 3005 3010 3015
Gly Ala Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3020 3025 3030 Thr Leu
Glu Asp Leu Lys Asn Glu Glu Met Val Thr Asn His Met 3035
3040 3045 Glu Gly Glu His Lys Lys Leu
Ala Glu Ala Ile Phe Lys Leu Thr 3050 3055
3060 Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Thr
Pro Arg Gly 3065 3070 3075
Thr Val Met Asp Ile Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly 3080
3085 3090 Gln Val Gly Thr Tyr
Gly Leu Asn Thr Phe Thr Asn Met Glu Ala 3095 3100
3105 Gln Leu Ile Arg Gln Met Glu Gly Glu Gly
Val Phe Lys Ser Ile 3110 3115 3120
Gln His Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu
3125 3130 3135 Ala Arg
Val Gly Arg Glu Arg Leu Ser Arg Met Ala Ile Ser Gly 3140
3145 3150 Asp Asp Cys Val Val Lys Pro
Leu Asp Asp Arg Phe Ala Ser Ala 3155 3160
3165 Leu Thr Ala Leu Asn Asp Met Gly Lys Ile Arg Lys
Asp Ile Gln 3170 3175 3180
Gln Trp Glu Pro Ser Arg Gly Trp Asn Asp Trp Thr Gln Val Pro 3185
3190 3195 Phe Cys Ser His His
Phe His Glu Leu Ile Met Lys Asp Gly Arg 3200 3205
3210 Val Leu Val Val Pro Cys Arg Asn Gln Asp
Glu Leu Ile Gly Arg 3215 3220 3225
Ala Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala
3230 3235 3240 Cys Leu
Gly Lys Ser Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe 3245
3250 3255 His Arg Arg Asp Leu Arg Leu
Ala Ala Asn Ala Ile Cys Ser Ala 3260 3265
3270 Val Pro Ser His Trp Val Pro Thr Ser Arg Thr Thr
Trp Ser Ile 3275 3280 3285
His Ala Lys His Glu Trp Met Thr Thr Glu Asp Met Leu Thr Val 3290
3295 3300 Trp Asn Arg Val Trp
Ile Gln Glu Asn Pro Trp Met Glu Asp Lys 3305 3310
3315 Thr Pro Val Glu Ser Trp Glu Glu Ile Pro
Tyr Leu Gly Lys Arg 3320 3325 3330
Glu Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala
3335 3340 3345 Thr Trp
Ala Lys Asn Ile Gln Ala Ala Ile Asn Gln Val Arg Ser 3350
3355 3360 Leu Ile Gly Asn Glu Glu Tyr
Thr Asp Tyr Met Pro Ser Met Lys 3365 3370
3375 Arg Phe Arg Arg Glu Glu Glu Glu Ala Gly Val Leu
Trp 3380 3385 3390
3010723DNAArtificial SequenceDerived from Dengue virus serotype 2/Dengue
virus serotype 4, Denvax-4f 30agttgttagt ctacgtggac cgacaaagac
agattctttg agggagctaa gctcaatgta 60gttctaacag ttttttaatt agagagcaga
tctctgatga ataaccaacg gaaaaaggcg 120aaaaacacgc ctttcaatat gctgaaacgc
gagagaaacc gcgtgtcgac tgtgcaacag 180ctgacaaaga gattctcact tggaatgctg
cagggacgag gaccattaaa actgttcatg 240gccctggtgg cgttccttcg tttcctaaca
atcccaccaa cagcagggat attgaagaga 300tggggaacaa ttaaaaaatc aaaagctatt
aatgttttga gagggttcag gaaagagatt 360ggaaggatgc tgaacatctt gaataggaga
cgcagctctg caggcatgat cattatgctg 420attccaacag tgatggcgtt ccatttaacc
acgcgtgatg gcgaacccct catgatagtg 480gcaaaacatg aaagggggag acctctcttg
tttaagacaa cagaggggat caacaaatgc 540actctcattg ccatggactt gggtgaaatg
tgtgaggaca ctgtcacgta taaatgcccc 600ttactggtca ataccgaacc tgaagacatt
gattgctggt gcaatctcac gtctacctgg 660gtcatgtatg ggacatgcac ccagagcgga
gaacggagac gagagaagcg ctcagtagct 720ttaacaccac attcaggaat gggattggaa
acaagagctg agacatggat gtcatcggaa 780ggggcttgga agcatgctca gagagtagag
agctggatac tcagaaaccc aggattcgcg 840ctcttggcag gatttatggc ttatatgatt
gggcaaacag gaatccagcg aactgtcttc 900tttgtcctaa tgatgctggt cgccccatcc
tacggaatgc gatgcgtagg agtaggaaac 960agagactttg tggaaggagt ctcaggtgga
gcatgggtcg atctggtgct agaacatgga 1020ggatgcgtca caaccatggc ccagggaaaa
ccaaccttgg attttgaact gactaagaca 1080acagccaagg aagtggctct gttaagaacc
tattgcattg aagcctcaat atcaaacata 1140accacggcaa caagatgtcc aacgcaagga
gagccttatc taaaagagga acaagaccaa 1200cagtacattt gccggagaga tgtggtagac
agagggtggg gcaatggctg tggcttgttt 1260ggaaaaggag gagttgtgac atgtgcgaag
ttttcatgtt cggggaagat aacaggcaat 1320ttggtccaaa ttgagaacct tgaatacaca
gtggttgtaa cagtccacaa tggagacacc 1380catgcagtag gaaatgacac gtccaatcat
ggagttacag ccacgataac tcccaggtca 1440ccatcggtgg aagtcaaatt gccggactat
ggagaactaa cactcgattg tgaacccagg 1500tctggaattg actttaatga gatgattctg
atgaaaatga aaaagaaaac atggcttgtg 1560cataagcaat ggtttttgga tctacctcta
ccatggacag caggagcaga cacatcagag 1620gttcactgga attacaaaga gagaatggtg
acatttaagg ttcctcatgc caagagacag 1680gatgtgacag tgctgggatc tcaggaagga
gccatgcatt ctgccctcgc tggagccaca 1740gaagtggact ccggtgatgg aaatcacatg
tttgcaggac atctcaagtg caaagtccgt 1800atggagaaat tgagaatcaa gggaatgtca
tacacgatgt gttcaggaaa gttctcaatt 1860gacaaagaga tggcagaaac acagcatggg
acaacagtgg tgaaagtcaa gtatgaaggt 1920gctggagctc cgtgtaaagt ccccatagag
ataagagatg tgaacaagga aaaagtggtt 1980gggcgtatca tctcatccac ccctttggct
gagaatacca acagtgtaac caacatagag 2040ttagaacccc cctttgggga cagctacata
gtgataggtg ttggaaacag tgcattaaca 2100ctccattggt tcaggaaagg gagttccatt
ggcaagatgt ttgagtccac atacagaggt 2160gcaaaacgaa tggccattct aggtgaaaca
gcttgggatt ttggttccgt tggtggactg 2220ttcacatcat tgggaaaggc tgtgcaccag
gtttttggaa gtgtgtatac aaccctgttt 2280ggaggagtct catggatgat tagaatccta
attgggttcc tagtgttgtg gattggcacg 2340aactcaagga acacttcaat ggctatgacg
tgcatagctg ccggcattgt gacactgtat 2400ttgggagtca tggtgcaggc cgatagtggt
tgcgttgtga gctggaaaaa caaagaactg 2460aaatgtggca gtgggatttt catcacagac
aacgtgcaca catggacaga acaatacaag 2520ttccaaccag aatccccttc aaaactagct
tcagctatcc agaaagccca tgaagaggac 2580atttgtggaa tccgctcagt aacaagactg
gagaatctga tgtggaaaca aataacacca 2640gaattgaatc acattctatc agaaaatgag
gtgaagttaa ctattatgac aggagacatc 2700aaaggaatca tgcaggcagg aaaacgatct
ctgcggcctc agcccactga gctgaagtat 2760tcatggaaaa catggggcaa agcaaaaatg
ctctctacag agtctcataa ccagaccttt 2820ctcattgatg gccccgaaac agcagaatgc
cccaacacaa atagagcttg gaattcgttg 2880gaagttgaag actatggctt tggagtattc
accaccaata tatggctaaa attgaaagaa 2940aaacaggatg tattctgcga ctcaaaactc
atgtcagcgg ccataaaaga caacagagcc 3000gtccatgccg atatgggtta ttggatagaa
agtgcactca atgacacatg gaagatagag 3060aaagcctctt tcattgaagt taaaaactgc
cactggccaa aatcacacac cctctggagc 3120aatggagtgc tagaaagtga gatgataatt
ccaaagaatc tcgctggacc agtgtctcaa 3180cacaactata gaccaggcta ccatacacaa
ataacaggac catggcatct aggtaagctt 3240gagatggact ttgatttctg tgatggaaca
acagtggtag tgactgagga ctgcggaaat 3300agaggaccct ctttgagaac aaccactgcc
tctggaaaac tcataacaga atggtgctgc 3360cgatcttgca cattaccacc gctaagatac
agaggtgagg atgggtgctg gtacgggatg 3420gaaatcagac cattgaagga gaaagaagag
aatttggtca actccttggt cacagctgga 3480catgggcagg tcgacaactt ttcactagga
gtcttgggaa tggcattgtt cctggaggaa 3540atgcttagga cccgagtagg aacgaaacat
gcaatactac tagttgcagt ttcttttgtg 3600acattgatca cagggaacat gtcctttaga
gacctgggaa gagtgatggt tatggtaggc 3660gccactatga cggatgacat aggtatgggc
gtgacttatc ttgccctact agcagccttc 3720aaagtcagac caacttttgc agctggacta
ctcttgagaa agctgacctc caaggaattg 3780atgatgacta ctataggaat tgtactcctc
tcccagagca ccataccaga gaccattctt 3840gagttgactg atgcgttagc cttaggcatg
atggtcctca aaatggtgag aaatatggaa 3900aagtatcaat tggcagtgac tatcatggct
atcttgtgcg tcccaaacgc agtgatatta 3960caaaacgcat ggaaagtgag ttgcacaata
ttggcagtgg tgtccgtttc cccactgctc 4020ttaacatcct cacagcaaaa aacagattgg
ataccattag cattgacgat caaaggtctc 4080aatccaacag ctatttttct aacaaccctc
tcaagaacca gcaagaaaag gagctggcca 4140ttaaatgagg ctatcatggc agtcgggatg
gtgagcattt tagccagttc tctcctaaaa 4200aatgatattc ccatgacagg accattagtg
gctggagggc tcctcactgt gtgctacgtg 4260ctcactggac gatcggccga tttggaactg
gagagagcag ccgatgtcaa atgggaagac 4320caggcagaga tatcaggaag cagtccaatc
ctgtcaataa caatatcaga agatggtagc 4380atgtcgataa aaaatgaaga ggaagaacaa
acactgacca tactcattag aacaggattg 4440ctggtgatct caggactttt tcctgtatca
ataccaatca cggcagcagc atggtacctg 4500tgggaagtga agaaacaacg ggccggagta
ttgtgggatg ttccttcacc cccacccatg 4560ggaaaggctg aactggaaga tggagcctat
agaattaagc aaaaagggat tcttggatat 4620tcccagatcg gagccggagt ttacaaagaa
ggaacattcc atacaatgtg gcatgtcaca 4680cgtggcgctg ttctaatgca taaaggaaag
aggattgaac catcatgggc ggacgtcaag 4740aaagacctaa tatcatatgg aggaggctgg
aagttagaag gagaatggaa ggaaggagaa 4800gaagtccagg tattggcact ggagcctgga
aaaaatccaa gagccgtcca aacgaaacct 4860ggtcttttca aaaccaacgc cggaacaata
ggtgctgtat ctctggactt ttctcctgga 4920acgtcaggat ctccaattat cgacaaaaaa
ggaaaagttg tgggtcttta tggtaatggt 4980gttgttacaa ggagtggagc atatgtgagt
gctatagccc agactgaaaa aagcattgaa 5040gacaacccag agatcgaaga tgacattttc
cgaaagagaa gactgaccat catggacctc 5100cacccaggag cgggaaagac gaagagatac
cttccggcca tagtcagaga agctataaaa 5160cggggtttga gaacattaat cttggccccc
actagagttg tggcagctga aatggaggaa 5220gcccttagag gacttccaat aagataccag
accccagcca tcagagctgt gcacaccggg 5280cgggagattg tggacctaat gtgtcatgcc
acatttacca tgaggctgct atcaccagtt 5340agagtgccaa actacaacct gattatcatg
gacgaagccc atttcacaga cccagcaagt 5400atagcagcta gaggatacat ctcaactcga
gtggagatgg gtgaggcagc tgggattttt 5460atgacagcca ctcccccggg aagcagagac
ccatttcctc agagcaatgc accaatcata 5520gatgaagaaa gagaaatccc tgaacgctcg
tggaattccg gacatgaatg ggtcacggat 5580tttaaaggga agactgtttg gttcgttcca
agtataaaag caggaaatga tatagcagct 5640tgcctgagga aaaatggaaa gaaagtgata
caactcagta ggaagacctt tgattctgag 5700tatgtcaaga ctagaaccaa tgattgggac
ttcgtggtta caactgacat ttcagaaatg 5760ggtgccaatt tcaaggctga gagggttata
gaccccagac gctgcatgaa accagtcata 5820ctaacagatg gtgaagagcg ggtgattctg
gcaggaccta tgccagtgac ccactctagt 5880gcagcacaaa gaagagggag aataggaaga
aatccaaaaa atgagaatga ccagtacata 5940tacatggggg aacctctgga aaatgatgaa
gactgtgcac actggaaaga agctaaaatg 6000ctcctagata acatcaacac gccagaagga
atcattccta gcatgttcga accagagcgt 6060gaaaaggtgg atgccattga tggcgaatac
cgcttgagag gagaagcaag gaaaaccttt 6120gtagacttaa tgagaagagg agacctacca
gtctggttgg cctacagagt ggcagctgaa 6180ggcatcaact acgcagacag aaggtggtgt
tttgatggag tcaagaacaa ccaaatccta 6240gaagaaaacg tggaagttga aatctggaca
aaagaagggg aaaggaagaa attgaaaccc 6300agatggttgg atgctaggat ctattctgac
ccactggcgc taaaagaatt taaggaattt 6360gcagccggaa gaaagtctct gaccctgaac
ctaatcacag aaatgggtag gctcccaacc 6420ttcatgactc agaaggcaag agacgcactg
gacaacttag cagtgctgca cacggctgag 6480gcaggtggaa gggcgtacaa ccatgctctc
agtgaactgc cggagaccct ggagacattg 6540cttttactga cacttctggc tacagtcacg
ggagggatct ttttattctt gatgagcgga 6600aggggcatag ggaagatgac cctgggaatg
tgctgcataa tcacggctag catcctccta 6660tggtacgcac aaatacagcc acactggata
gcagcttcaa taatactgga gttttttctc 6720atagttttgc ttattccaga acctgaaaaa
cagagaacac cccaagacaa ccaactgacc 6780tacgttgtca tagccatcct cacagtggtg
gccgcaacca tggcaaacga gatgggtttc 6840ctagaaaaaa cgaagaaaga tctcggattg
ggaagcattg caacccagca acccgagagc 6900aacatcctgg acatagatct acgtcctgca
tcagcatgga cgctgtatgc cgtggccaca 6960acatttgtta caccaatgtt gagacatagc
attgaaaatt cctcagtgaa tgtgtcccta 7020acagctatag ccaaccaagc cacagtgtta
atgggtctcg ggaaaggatg gccattgtca 7080aagatggaca tcggagttcc ccttctcgcc
attggatgct actcacaagt caaccccata 7140actctcacag cagctctttt cttattggta
gcacattatg ccatcatagg gccaggactc 7200caagcaaaag caaccagaga agctcagaaa
agagcagcgg cgggcatcat gaaaaaccca 7260actgtcgatg gaataacagt gattgaccta
gatccaatac cttatgatcc aaagtttgaa 7320aagcagttgg gacaagtaat gctcctagtc
ctctgcgtga ctcaagtatt gatgatgagg 7380actacatggg ctctgtgtga ggctttaacc
ttagctaccg ggcccatctc cacattgtgg 7440gaaggaaatc cagggaggtt ttggaacact
accattgcgg tgtcaatggc taacattttt 7500agagggagtt acttggccgg agctggactt
ctcttttcta ttatgaagaa cacaaccaac 7560acaagaaggg gaactggcaa cataggagag
acgcttggag agaaatggaa aagccgattg 7620aacgcattgg gaaaaagtga attccagatc
tacaagaaaa gtggaatcca ggaagtggat 7680agaaccttag caaaagaagg cattaaaaga
ggagaaacgg accatcacgc tgtgtcgcga 7740ggctcagcaa aactgagatg gttcgttgag
agaaacatgg tcacaccaga agggaaagta 7800gtggacctcg gttgtggcag aggaggctgg
tcatactatt gtggaggact aaagaatgta 7860agagaagtca aaggcctaac aaaaggagga
ccaggacacg aagaacccat ccccatgtca 7920acatatgggt ggaatctagt gcgtcttcaa
agtggagttg acgttttctt catcccgcca 7980gaaaagtgtg acacattatt gtgtgacata
ggggagtcat caccaaatcc cacagtggaa 8040gcaggacgaa cactcagagt ccttaactta
gtagaaaatt ggttgaacaa caacactcaa 8100ttttgcataa aggttctcaa cccatatatg
ccctcagtca tagaaaaaat ggaagcacta 8160caaaggaaat atggaggagc cttagtgagg
aatccactct cacgaaactc cacacatgag 8220atgtactggg tatccaatgc ttccgggaac
atagtgtcat cagtgaacat gatttcaagg 8280atgttgatca acagatttac aatgagatac
aagaaagcca cttacgagcc ggatgttgac 8340ctcggaagcg gaacccgtaa catcgggatt
gaaagtgaga taccaaacct agatataatt 8400gggaaaagaa tagaaaaaat aaagcaagag
catgaaacat catggcacta tgaccaagac 8460cacccataca aaacgtgggc ataccatggt
agctatgaaa caaaacagac tggatcagca 8520tcatccatgg tcaacggagt ggtcaggctg
ctgacaaaac cttgggacgt cgtccccatg 8580gtgacacaga tggcaatgac agacacgact
ccatttggac aacagcgcgt ttttaaagag 8640aaagtggaca cgagaaccca agaaccgaaa
gaaggcacga agaaactaat gaaaataaca 8700gcagagtggc tttggaaaga attagggaag
aaaaagacac ccaggatgtg caccagagaa 8760gaattcacaa gaaaggtgag aagcaatgca
gccttggggg ccatattcac tgatgagaac 8820aagtggaagt cggcacgtga ggctgttgaa
gatagtaggt tttgggagct ggttgacaag 8880gaaaggaatc tccatcttga aggaaagtgt
gaaacatgtg tgtacaacat gatgggaaaa 8940agagagaaga agctagggga attcggcaag
gcaaaaggca gcagagccat atggtacatg 9000tggcttggag cacgcttctt agagtttgaa
gccctaggat tcttaaatga agatcactgg 9060ttctccagag agaactccct gagtggagtg
gaaggagaag ggctgcacaa gctaggttac 9120attctaagag acgtgagcaa gaaagaggga
ggagcaatgt atgccgatga caccgcagga 9180tgggatacaa gaatcacact agaagaccta
aaaaatgaag aaatggtaac aaaccacatg 9240gaaggagaac acaagaaact agccgaggcc
attttcaaac taacgtacca aaacaaggtg 9300gtgcgtgtgc aaagaccaac accaagaggc
acagtaatgg acatcatatc gagaagagac 9360caaagaggta gtggacaagt tggcacctat
ggactcaata ctttcaccaa tatggaagcc 9420caactaatca gacagatgga gggagaagga
gtctttaaaa gcattcagca cctaacaatc 9480acagaagaaa tcgctgtgca aaactggtta
gcaagagtgg ggcgcgaaag gttatcaaga 9540atggccatca gtggagatga ttgtgttgtg
aaacctttag atgacaggtt cgcaagcgct 9600ttaacagctc taaatgacat gggaaagatt
aggaaagaca tacaacaatg ggaaccttca 9660agaggatgga atgattggac acaagtgccc
ttctgttcac accatttcca tgagttaatc 9720atgaaagacg gtcgcgtact cgttgttcca
tgtagaaacc aagatgaact gattggcaga 9780gcccgaatct cccaaggagc agggtggtct
ttgcgggaga cggcctgttt ggggaagtct 9840tacgcccaaa tgtggagctt gatgtacttc
cacagacgcg acctcaggct ggcggcaaat 9900gctatttgct cggcagtacc atcacattgg
gttccaacaa gtcgaacaac ctggtccata 9960catgctaaac atgaatggat gacaacggaa
gacatgctga cagtctggaa cagggtgtgg 10020attcaagaaa acccatggat ggaagacaaa
actccagtgg aatcatggga ggaaatccca 10080tacttgggga aaagagaaga ccaatggtgc
ggctcattga ttgggttaac aagcagggcc 10140acctgggcaa agaacatcca agcagcaata
aatcaagtta gatcccttat aggcaatgaa 10200gaatacacag attacatgcc atccatgaaa
agattcagaa gagaagagga agaagcagga 10260gttctgtggt agaaagcaaa actaacatga
aacaaggcta gaagtcaggt cggattaagc 10320catagtacgg aaaaaactat gctacctgtg
agccccgtcc aaggacgtta aaagaagtca 10380ggccatcata aatgccatag cttgagtaaa
ctatgcagcc tgtagctcca cctgagaagg 10440tgtaaaaaat ccgggaggcc acaaaccatg
gaagctgtac gcatggcgta gtggactagc 10500ggttagagga gacccctccc ttacaaatcg
cagcaacaat gggggcccaa ggcgagatga 10560agctgtagtc tcgctggaag gactagaggt
tagaggagac ccccccgaaa caaaaaacag 10620catattgacg ctgggaaaga ccagagatcc
tgctgtctcc tcagcatcat tccaggcaca 10680gaacgccaga aaatggaatg gtgctgttga
atcaacaggt tct 10723313391PRTArtificial
SequenceDerived from Dengue virus serotype 2/Dengue virus serotype
4, DenVax-4f 31Met Asn Asn Gln Arg Lys Lys Ala Lys Asn Thr Pro Phe Asn
Met Leu 1 5 10 15
Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln Gln Leu Thr Lys Arg
20 25 30 Phe Ser Leu Gly Met
Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe Met 35
40 45 Ala Leu Val Ala Phe Leu Arg Phe Leu
Thr Ile Pro Pro Thr Ala Gly 50 55
60 Ile Leu Lys Arg Trp Gly Thr Ile Lys Lys Ser Lys Ala
Ile Asn Val 65 70 75
80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met Leu Asn Ile Leu Asn
85 90 95 Arg Arg Arg Ser
Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val 100
105 110 Met Ala Phe His Leu Thr Thr Arg Asp
Gly Glu Pro Leu Met Ile Val 115 120
125 Ala Lys His Glu Arg Gly Arg Pro Leu Leu Phe Lys Thr Thr
Glu Gly 130 135 140
Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly Glu Met Cys Glu 145
150 155 160 Asp Thr Val Thr Tyr
Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu 165
170 175 Asp Ile Asp Cys Trp Cys Asn Leu Thr Ser
Thr Trp Val Met Tyr Gly 180 185
190 Thr Cys Thr Gln Ser Gly Glu Arg Arg Arg Glu Lys Arg Ser Val
Ala 195 200 205 Leu
Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala Glu Thr Trp 210
215 220 Met Ser Ser Glu Gly Ala
Trp Lys His Ala Gln Arg Val Glu Ser Trp 225 230
235 240 Ile Leu Arg Asn Pro Gly Phe Ala Leu Leu Ala
Gly Phe Met Ala Tyr 245 250
255 Met Ile Gly Gln Thr Gly Ile Gln Arg Thr Val Phe Phe Val Leu Met
260 265 270 Met Leu
Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val Gly Asn 275
280 285 Arg Asp Phe Val Glu Gly Val
Ser Gly Gly Ala Trp Val Asp Leu Val 290 295
300 Leu Glu His Gly Gly Cys Val Thr Thr Met Ala Gln
Gly Lys Pro Thr 305 310 315
320 Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala Lys Glu Val Ala Leu Leu
325 330 335 Arg Thr Tyr
Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala Thr 340
345 350 Arg Cys Pro Thr Gln Gly Glu Pro
Tyr Leu Lys Glu Glu Gln Asp Gln 355 360
365 Gln Tyr Ile Cys Arg Arg Asp Val Val Asp Arg Gly Trp
Gly Asn Gly 370 375 380
Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr Cys Ala Lys Phe Ser 385
390 395 400 Cys Ser Gly Lys
Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu 405
410 415 Tyr Thr Val Val Val Thr Val His Asn
Gly Asp Thr His Ala Val Gly 420 425
430 Asn Asp Thr Ser Asn His Gly Val Thr Ala Thr Ile Thr Pro
Arg Ser 435 440 445
Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu Leu Thr Leu Asp 450
455 460 Cys Glu Pro Arg Ser
Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys 465 470
475 480 Met Lys Lys Lys Thr Trp Leu Val His Lys
Gln Trp Phe Leu Asp Leu 485 490
495 Pro Leu Pro Trp Thr Ala Gly Ala Asp Thr Ser Glu Val His Trp
Asn 500 505 510 Tyr
Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala Lys Arg Gln 515
520 525 Asp Val Thr Val Leu Gly
Ser Gln Glu Gly Ala Met His Ser Ala Leu 530 535
540 Ala Gly Ala Thr Glu Val Asp Ser Gly Asp Gly
Asn His Met Phe Ala 545 550 555
560 Gly His Leu Lys Cys Lys Val Arg Met Glu Lys Leu Arg Ile Lys Gly
565 570 575 Met Ser
Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys Glu Met 580
585 590 Ala Glu Thr Gln His Gly Thr
Thr Val Val Lys Val Lys Tyr Glu Gly 595 600
605 Ala Gly Ala Pro Cys Lys Val Pro Ile Glu Ile Arg
Asp Val Asn Lys 610 615 620
Glu Lys Val Val Gly Arg Ile Ile Ser Ser Thr Pro Leu Ala Glu Asn 625
630 635 640 Thr Asn Ser
Val Thr Asn Ile Glu Leu Glu Pro Pro Phe Gly Asp Ser 645
650 655 Tyr Ile Val Ile Gly Val Gly Asn
Ser Ala Leu Thr Leu His Trp Phe 660 665
670 Arg Lys Gly Ser Ser Ile Gly Lys Met Phe Glu Ser Thr
Tyr Arg Gly 675 680 685
Ala Lys Arg Met Ala Ile Leu Gly Glu Thr Ala Trp Asp Phe Gly Ser 690
695 700 Val Gly Gly Leu
Phe Thr Ser Leu Gly Lys Ala Val His Gln Val Phe 705 710
715 720 Gly Ser Val Tyr Thr Thr Leu Phe Gly
Gly Val Ser Trp Met Ile Arg 725 730
735 Ile Leu Ile Gly Phe Leu Val Leu Trp Ile Gly Thr Asn Ser
Arg Asn 740 745 750
Thr Ser Met Ala Met Thr Cys Ile Ala Ala Gly Ile Val Thr Leu Tyr
755 760 765 Leu Gly Val Met
Val Gln Ala Asp Ser Gly Cys Val Val Ser Trp Lys 770
775 780 Asn Lys Glu Leu Lys Cys Gly Ser
Gly Ile Phe Ile Thr Asp Asn Val 785 790
795 800 His Thr Trp Thr Glu Gln Tyr Lys Phe Gln Pro Glu
Ser Pro Ser Lys 805 810
815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu Glu Asp Ile Cys Gly Ile
820 825 830 Arg Ser Val
Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr Pro 835
840 845 Glu Leu Asn His Ile Leu Ser Glu
Asn Glu Val Lys Leu Thr Ile Met 850 855
860 Thr Gly Asp Ile Lys Gly Ile Met Gln Ala Gly Lys Arg
Ser Leu Arg 865 870 875
880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys Thr Trp Gly Lys Ala
885 890 895 Lys Met Leu Ser
Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly 900
905 910 Pro Glu Thr Ala Glu Cys Pro Asn Thr
Asn Arg Ala Trp Asn Ser Leu 915 920
925 Glu Val Glu Asp Tyr Gly Phe Gly Val Phe Thr Thr Asn Ile
Trp Leu 930 935 940
Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser Lys Leu Met Ser 945
950 955 960 Ala Ala Ile Lys Asp
Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp 965
970 975 Ile Glu Ser Ala Leu Asn Asp Thr Trp Lys
Ile Glu Lys Ala Ser Phe 980 985
990 Ile Glu Val Lys Asn Cys His Trp Pro Lys Ser His Thr Leu
Trp Ser 995 1000 1005
Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro Lys Asn Leu Ala 1010
1015 1020 Gly Pro Val Ser Gln
His Asn Tyr Arg Pro Gly Tyr His Thr Gln 1025 1030
1035 Ile Thr Gly Pro Trp His Leu Gly Lys Leu
Glu Met Asp Phe Asp 1040 1045 1050
Phe Cys Asp Gly Thr Thr Val Val Val Thr Glu Asp Cys Gly Asn
1055 1060 1065 Arg Gly
Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys Leu Ile 1070
1075 1080 Thr Glu Trp Cys Cys Arg Ser
Cys Thr Leu Pro Pro Leu Arg Tyr 1085 1090
1095 Arg Gly Glu Asp Gly Cys Trp Tyr Gly Met Glu Ile
Arg Pro Leu 1100 1105 1110
Lys Glu Lys Glu Glu Asn Leu Val Asn Ser Leu Val Thr Ala Gly 1115
1120 1125 His Gly Gln Val Asp
Asn Phe Ser Leu Gly Val Leu Gly Met Ala 1130 1135
1140 Leu Phe Leu Glu Glu Met Leu Arg Thr Arg
Val Gly Thr Lys His 1145 1150 1155
Ala Ile Leu Leu Val Ala Val Ser Phe Val Thr Leu Ile Thr Gly
1160 1165 1170 Asn Met
Ser Phe Arg Asp Leu Gly Arg Val Met Val Met Val Gly 1175
1180 1185 Ala Thr Met Thr Asp Asp Ile
Gly Met Gly Val Thr Tyr Leu Ala 1190 1195
1200 Leu Leu Ala Ala Phe Lys Val Arg Pro Thr Phe Ala
Ala Gly Leu 1205 1210 1215
Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu Met Met Thr Thr Ile 1220
1225 1230 Gly Ile Val Leu Leu
Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu 1235 1240
1245 Glu Leu Thr Asp Ala Leu Ala Leu Gly Met
Met Val Leu Lys Met 1250 1255 1260
Val Arg Asn Met Glu Lys Tyr Gln Leu Ala Val Thr Ile Met Ala
1265 1270 1275 Ile Leu
Cys Val Pro Asn Ala Val Ile Leu Gln Asn Ala Trp Lys 1280
1285 1290 Val Ser Cys Thr Ile Leu Ala
Val Val Ser Val Ser Pro Leu Leu 1295 1300
1305 Leu Thr Ser Ser Gln Gln Lys Thr Asp Trp Ile Pro
Leu Ala Leu 1310 1315 1320
Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile Phe Leu Thr Thr Leu 1325
1330 1335 Ser Arg Thr Ser Lys
Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile 1340 1345
1350 Met Ala Val Gly Met Val Ser Ile Leu Ala
Ser Ser Leu Leu Lys 1355 1360 1365
Asn Asp Ile Pro Met Thr Gly Pro Leu Val Ala Gly Gly Leu Leu
1370 1375 1380 Thr Val
Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp Leu Glu Leu 1385
1390 1395 Glu Arg Ala Ala Asp Val Lys
Trp Glu Asp Gln Ala Glu Ile Ser 1400 1405
1410 Gly Ser Ser Pro Ile Leu Ser Ile Thr Ile Ser Glu
Asp Gly Ser 1415 1420 1425
Met Ser Ile Lys Asn Glu Glu Glu Glu Gln Thr Leu Thr Ile Leu 1430
1435 1440 Ile Arg Thr Gly Leu
Leu Val Ile Ser Gly Leu Phe Pro Val Ser 1445 1450
1455 Ile Pro Ile Thr Ala Ala Ala Trp Tyr Leu
Trp Glu Val Lys Lys 1460 1465 1470
Gln Arg Ala Gly Val Leu Trp Asp Val Pro Ser Pro Pro Pro Met
1475 1480 1485 Gly Lys
Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile Lys Gln Lys 1490
1495 1500 Gly Ile Leu Gly Tyr Ser Gln
Ile Gly Ala Gly Val Tyr Lys Glu 1505 1510
1515 Gly Thr Phe His Thr Met Trp His Val Thr Arg Gly
Ala Val Leu 1520 1525 1530
Met His Lys Gly Lys Arg Ile Glu Pro Ser Trp Ala Asp Val Lys 1535
1540 1545 Lys Asp Leu Ile Ser
Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu 1550 1555
1560 Trp Lys Glu Gly Glu Glu Val Gln Val Leu
Ala Leu Glu Pro Gly 1565 1570 1575
Lys Asn Pro Arg Ala Val Gln Thr Lys Pro Gly Leu Phe Lys Thr
1580 1585 1590 Asn Ala
Gly Thr Ile Gly Ala Val Ser Leu Asp Phe Ser Pro Gly 1595
1600 1605 Thr Ser Gly Ser Pro Ile Ile
Asp Lys Lys Gly Lys Val Val Gly 1610 1615
1620 Leu Tyr Gly Asn Gly Val Val Thr Arg Ser Gly Ala
Tyr Val Ser 1625 1630 1635
Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu Asp Asn Pro Glu Ile 1640
1645 1650 Glu Asp Asp Ile Phe
Arg Lys Arg Arg Leu Thr Ile Met Asp Leu 1655 1660
1665 His Pro Gly Ala Gly Lys Thr Lys Arg Tyr
Leu Pro Ala Ile Val 1670 1675 1680
Arg Glu Ala Ile Lys Arg Gly Leu Arg Thr Leu Ile Leu Ala Pro
1685 1690 1695 Thr Arg
Val Val Ala Ala Glu Met Glu Glu Ala Leu Arg Gly Leu 1700
1705 1710 Pro Ile Arg Tyr Gln Thr Pro
Ala Ile Arg Ala Val His Thr Gly 1715 1720
1725 Arg Glu Ile Val Asp Leu Met Cys His Ala Thr Phe
Thr Met Arg 1730 1735 1740
Leu Leu Ser Pro Val Arg Val Pro Asn Tyr Asn Leu Ile Ile Met 1745
1750 1755 Asp Glu Ala His Phe
Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly 1760 1765
1770 Tyr Ile Ser Thr Arg Val Glu Met Gly Glu
Ala Ala Gly Ile Phe 1775 1780 1785
Met Thr Ala Thr Pro Pro Gly Ser Arg Asp Pro Phe Pro Gln Ser
1790 1795 1800 Asn Ala
Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro Glu Arg Ser 1805
1810 1815 Trp Asn Ser Gly His Glu Trp
Val Thr Asp Phe Lys Gly Lys Thr 1820 1825
1830 Val Trp Phe Val Pro Ser Ile Lys Ala Gly Asn Asp
Ile Ala Ala 1835 1840 1845
Cys Leu Arg Lys Asn Gly Lys Lys Val Ile Gln Leu Ser Arg Lys 1850
1855 1860 Thr Phe Asp Ser Glu
Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp 1865 1870
1875 Phe Val Val Thr Thr Asp Ile Ser Glu Met
Gly Ala Asn Phe Lys 1880 1885 1890
Ala Glu Arg Val Ile Asp Pro Arg Arg Cys Met Lys Pro Val Ile
1895 1900 1905 Leu Thr
Asp Gly Glu Glu Arg Val Ile Leu Ala Gly Pro Met Pro 1910
1915 1920 Val Thr His Ser Ser Ala Ala
Gln Arg Arg Gly Arg Ile Gly Arg 1925 1930
1935 Asn Pro Lys Asn Glu Asn Asp Gln Tyr Ile Tyr Met
Gly Glu Pro 1940 1945 1950
Leu Glu Asn Asp Glu Asp Cys Ala His Trp Lys Glu Ala Lys Met 1955
1960 1965 Leu Leu Asp Asn Ile
Asn Thr Pro Glu Gly Ile Ile Pro Ser Met 1970 1975
1980 Phe Glu Pro Glu Arg Glu Lys Val Asp Ala
Ile Asp Gly Glu Tyr 1985 1990 1995
Arg Leu Arg Gly Glu Ala Arg Lys Thr Phe Val Asp Leu Met Arg
2000 2005 2010 Arg Gly
Asp Leu Pro Val Trp Leu Ala Tyr Arg Val Ala Ala Glu 2015
2020 2025 Gly Ile Asn Tyr Ala Asp Arg
Arg Trp Cys Phe Asp Gly Val Lys 2030 2035
2040 Asn Asn Gln Ile Leu Glu Glu Asn Val Glu Val Glu
Ile Trp Thr 2045 2050 2055
Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro Arg Trp Leu Asp Ala 2060
2065 2070 Arg Ile Tyr Ser Asp
Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe 2075 2080
2085 Ala Ala Gly Arg Lys Ser Leu Thr Leu Asn
Leu Ile Thr Glu Met 2090 2095 2100
Gly Arg Leu Pro Thr Phe Met Thr Gln Lys Ala Arg Asp Ala Leu
2105 2110 2115 Asp Asn
Leu Ala Val Leu His Thr Ala Glu Ala Gly Gly Arg Ala 2120
2125 2130 Tyr Asn His Ala Leu Ser Glu
Leu Pro Glu Thr Leu Glu Thr Leu 2135 2140
2145 Leu Leu Leu Thr Leu Leu Ala Thr Val Thr Gly Gly
Ile Phe Leu 2150 2155 2160
Phe Leu Met Ser Gly Arg Gly Ile Gly Lys Met Thr Leu Gly Met 2165
2170 2175 Cys Cys Ile Ile Thr
Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile 2180 2185
2190 Gln Pro His Trp Ile Ala Ala Ser Ile Ile
Leu Glu Phe Phe Leu 2195 2200 2205
Ile Val Leu Leu Ile Pro Glu Pro Glu Lys Gln Arg Thr Pro Gln
2210 2215 2220 Asp Asn
Gln Leu Thr Tyr Val Val Ile Ala Ile Leu Thr Val Val 2225
2230 2235 Ala Ala Thr Met Ala Asn Glu
Met Gly Phe Leu Glu Lys Thr Lys 2240 2245
2250 Lys Asp Leu Gly Leu Gly Ser Ile Ala Thr Gln Gln
Pro Glu Ser 2255 2260 2265
Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala Ser Ala Trp Thr Leu 2270
2275 2280 Tyr Ala Val Ala Thr
Thr Phe Val Thr Pro Met Leu Arg His Ser 2285 2290
2295 Ile Glu Asn Ser Ser Val Asn Val Ser Leu
Thr Ala Ile Ala Asn 2300 2305 2310
Gln Ala Thr Val Leu Met Gly Leu Gly Lys Gly Trp Pro Leu Ser
2315 2320 2325 Lys Met
Asp Ile Gly Val Pro Leu Leu Ala Ile Gly Cys Tyr Ser 2330
2335 2340 Gln Val Asn Pro Ile Thr Leu
Thr Ala Ala Leu Phe Leu Leu Val 2345 2350
2355 Ala His Tyr Ala Ile Ile Gly Pro Gly Leu Gln Ala
Lys Ala Thr 2360 2365 2370
Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly Ile Met Lys Asn Pro 2375
2380 2385 Thr Val Asp Gly Ile
Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr 2390 2395
2400 Asp Pro Lys Phe Glu Lys Gln Leu Gly Gln
Val Met Leu Leu Val 2405 2410 2415
Leu Cys Val Thr Gln Val Leu Met Met Arg Thr Thr Trp Ala Leu
2420 2425 2430 Cys Glu
Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser Thr Leu Trp 2435
2440 2445 Glu Gly Asn Pro Gly Arg Phe
Trp Asn Thr Thr Ile Ala Val Ser 2450 2455
2460 Met Ala Asn Ile Phe Arg Gly Ser Tyr Leu Ala Gly
Ala Gly Leu 2465 2470 2475
Leu Phe Ser Ile Met Lys Asn Thr Thr Asn Thr Arg Arg Gly Thr 2480
2485 2490 Gly Asn Ile Gly Glu
Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu 2495 2500
2505 Asn Ala Leu Gly Lys Ser Glu Phe Gln Ile
Tyr Lys Lys Ser Gly 2510 2515 2520
Ile Gln Glu Val Asp Arg Thr Leu Ala Lys Glu Gly Ile Lys Arg
2525 2530 2535 Gly Glu
Thr Asp His His Ala Val Ser Arg Gly Ser Ala Lys Leu 2540
2545 2550 Arg Trp Phe Val Glu Arg Asn
Met Val Thr Pro Glu Gly Lys Val 2555 2560
2565 Val Asp Leu Gly Cys Gly Arg Gly Gly Trp Ser Tyr
Tyr Cys Gly 2570 2575 2580
Gly Leu Lys Asn Val Arg Glu Val Lys Gly Leu Thr Lys Gly Gly 2585
2590 2595 Pro Gly His Glu Glu
Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn 2600 2605
2610 Leu Val Arg Leu Gln Ser Gly Val Asp Val
Phe Phe Ile Pro Pro 2615 2620 2625
Glu Lys Cys Asp Thr Leu Leu Cys Asp Ile Gly Glu Ser Ser Pro
2630 2635 2640 Asn Pro
Thr Val Glu Ala Gly Arg Thr Leu Arg Val Leu Asn Leu 2645
2650 2655 Val Glu Asn Trp Leu Asn Asn
Asn Thr Gln Phe Cys Ile Lys Val 2660 2665
2670 Leu Asn Pro Tyr Met Pro Ser Val Ile Glu Lys Met
Glu Ala Leu 2675 2680 2685
Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg Asn Pro Leu Ser Arg 2690
2695 2700 Asn Ser Thr His Glu
Met Tyr Trp Val Ser Asn Ala Ser Gly Asn 2705 2710
2715 Ile Val Ser Ser Val Asn Met Ile Ser Arg
Met Leu Ile Asn Arg 2720 2725 2730
Phe Thr Met Arg Tyr Lys Lys Ala Thr Tyr Glu Pro Asp Val Asp
2735 2740 2745 Leu Gly
Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser Glu Ile Pro 2750
2755 2760 Asn Leu Asp Ile Ile Gly Lys
Arg Ile Glu Lys Ile Lys Gln Glu 2765 2770
2775 His Glu Thr Ser Trp His Tyr Asp Gln Asp His Pro
Tyr Lys Thr 2780 2785 2790
Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys Gln Thr Gly Ser Ala 2795
2800 2805 Ser Ser Met Val Asn
Gly Val Val Arg Leu Leu Thr Lys Pro Trp 2810 2815
2820 Asp Val Val Pro Met Val Thr Gln Met Ala
Met Thr Asp Thr Thr 2825 2830 2835
Pro Phe Gly Gln Gln Arg Val Phe Lys Glu Lys Val Asp Thr Arg
2840 2845 2850 Thr Gln
Glu Pro Lys Glu Gly Thr Lys Lys Leu Met Lys Ile Thr 2855
2860 2865 Ala Glu Trp Leu Trp Lys Glu
Leu Gly Lys Lys Lys Thr Pro Arg 2870 2875
2880 Met Cys Thr Arg Glu Glu Phe Thr Arg Lys Val Arg
Ser Asn Ala 2885 2890 2895
Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn Lys Trp Lys Ser Ala 2900
2905 2910 Arg Glu Ala Val Glu
Asp Ser Arg Phe Trp Glu Leu Val Asp Lys 2915 2920
2925 Glu Arg Asn Leu His Leu Glu Gly Lys Cys
Glu Thr Cys Val Tyr 2930 2935 2940
Asn Met Met Gly Lys Arg Glu Lys Lys Leu Gly Glu Phe Gly Lys
2945 2950 2955 Ala Lys
Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu Gly Ala Arg 2960
2965 2970 Phe Leu Glu Phe Glu Ala Leu
Gly Phe Leu Asn Glu Asp His Trp 2975 2980
2985 Phe Ser Arg Glu Asn Ser Leu Ser Gly Val Glu Gly
Glu Gly Leu 2990 2995 3000
His Lys Leu Gly Tyr Ile Leu Arg Asp Val Ser Lys Lys Glu Gly 3005
3010 3015 Gly Ala Met Tyr Ala
Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile 3020 3025
3030 Thr Leu Glu Asp Leu Lys Asn Glu Glu Met
Val Thr Asn His Met 3035 3040 3045
Glu Gly Glu His Lys Lys Leu Ala Glu Ala Ile Phe Lys Leu Thr
3050 3055 3060 Tyr Gln
Asn Lys Val Val Arg Val Gln Arg Pro Thr Pro Arg Gly 3065
3070 3075 Thr Val Met Asp Ile Ile Ser
Arg Arg Asp Gln Arg Gly Ser Gly 3080 3085
3090 Gln Val Gly Thr Tyr Gly Leu Asn Thr Phe Thr Asn
Met Glu Ala 3095 3100 3105
Gln Leu Ile Arg Gln Met Glu Gly Glu Gly Val Phe Lys Ser Ile 3110
3115 3120 Gln His Leu Thr Ile
Thr Glu Glu Ile Ala Val Gln Asn Trp Leu 3125 3130
3135 Ala Arg Val Gly Arg Glu Arg Leu Ser Arg
Met Ala Ile Ser Gly 3140 3145 3150
Asp Asp Cys Val Val Lys Pro Leu Asp Asp Arg Phe Ala Ser Ala
3155 3160 3165 Leu Thr
Ala Leu Asn Asp Met Gly Lys Ile Arg Lys Asp Ile Gln 3170
3175 3180 Gln Trp Glu Pro Ser Arg Gly
Trp Asn Asp Trp Thr Gln Val Pro 3185 3190
3195 Phe Cys Ser His His Phe His Glu Leu Ile Met Lys
Asp Gly Arg 3200 3205 3210
Val Leu Val Val Pro Cys Arg Asn Gln Asp Glu Leu Ile Gly Arg 3215
3220 3225 Ala Arg Ile Ser Gln
Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala 3230 3235
3240 Cys Leu Gly Lys Ser Tyr Ala Gln Met Trp
Ser Leu Met Tyr Phe 3245 3250 3255
His Arg Arg Asp Leu Arg Leu Ala Ala Asn Ala Ile Cys Ser Ala
3260 3265 3270 Val Pro
Ser His Trp Val Pro Thr Ser Arg Thr Thr Trp Ser Ile 3275
3280 3285 His Ala Lys His Glu Trp Met
Thr Thr Glu Asp Met Leu Thr Val 3290 3295
3300 Trp Asn Arg Val Trp Ile Gln Glu Asn Pro Trp Met
Glu Asp Lys 3305 3310 3315
Thr Pro Val Glu Ser Trp Glu Glu Ile Pro Tyr Leu Gly Lys Arg 3320
3325 3330 Glu Asp Gln Trp Cys
Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala 3335 3340
3345 Thr Trp Ala Lys Asn Ile Gln Ala Ala Ile
Asn Gln Val Arg Ser 3350 3355 3360
Leu Ile Gly Asn Glu Glu Tyr Thr Asp Tyr Met Pro Ser Met Lys
3365 3370 3375 Arg Phe
Arg Arg Glu Glu Glu Glu Ala Gly Val Leu Trp 3380
3385 3390 3210723DNAArtificial SequenceDerived from
Dengue virus serotype 2/Dengue virus serotype 4, DenVax-4j
32agttgttagt ctacgtggac cgacaaagac agattctttg agggagctaa gctcaacgta
60gttctaacag ttttttaatt agagagcaga tctctgatga ataaccaacg gaaaaaggcg
120aaaaacacgc ctttcaatat gctgaaacgc gagagaaacc gcgtgtcgac tgtgcaacag
180ctgacaaaga gattctcact tggaatgctg cagggacgag gaccattaaa actgttcatg
240gccctggtgg cgttccttcg tttcctaaca atcccaccaa cagcagggat attgaagaga
300tggggaacaa ttaaaaaatc aaaagctatt aatgttttga gagggttcag gaaagagatt
360ggaaggatgc tgaacatctt gaataggaga cgcagctctg caggcatgat cattatgctg
420attccaacag tgatggcgtt ccatttaacc acgcgtgatg gcgaacccct catgatagtg
480gcaaaacatg aaagggggag acctctcttg tttaagacaa cagaggggat caacaaatgc
540actctcattg ccatggactt gggtgaaatg tgtgaggaca ctgtcacgta taaatgcccc
600ttactggtca ataccgaacc tgaagacatt gattgctggt gcaatctcac gtctacctgg
660gtcatgtatg ggacatgcac ccagagcgga gaacggagac gagagaagcg ctcagtagct
720ttaacaccac attcaggaat gggattggaa acaagagctg agacatggat gtcatcggaa
780ggggcttgga agcatgctca gagagtagag agctggatac tcagaaaccc aggattcgcg
840ctcttggcag gatttatggc ttatatgatt gggcaaacag gaatccagcg aactgtcttc
900tttgtcctaa tgatgctggt cgccccatcc tacggaatgc gatgcgtagg agtaggaaac
960agagactttg tggaaggagt ctcaggtgga gcatgggtcg atctggtgct agaacatgga
1020ggatgcgtca caaccatggc ccagggaaaa ccaaccttgg attttgaact gactaagaca
1080acagccaagg aagtggctct gttaagaacc tattgcattg aagcctcaat atcaaacata
1140accacggcaa caagatgtcc aacgcaagga gagccttatc taaaagagga acaagaccaa
1200cagtacattt gccggagaga tgtggtagac agagggtggg gcaatggctg tggcttgttt
1260ggaaaaggag gagttgtgac atgtgcgaag ttttcatgtt cggggaagat aacaggcaat
1320ttggtccaaa ttgagaacct tgaatacaca gtggttgtaa cagtccacaa tggagacacc
1380catgcagtag gaaatgacac gtccaatcat ggagttacag ccacgataac tcccaggtca
1440ccatcggtgg aagtcaaatt gccggactat ggagaactaa cactcgattg tgaacccagg
1500tctggaattg actttaatga gatgattctg atgaaaatga aaaagaaaac atggcttgtg
1560cataagcaat ggtttttgga tctacctcta ccatggacag caggagcaga cacatcagag
1620gttcactgga attacaaaga gagaatggtg acatttaagg ttcctcatgc caagagacag
1680gatgtgacag tgctgggatc tcaggaagga gccatgcatt ctgccctcgc tggagccaca
1740gaagtggact ccggtgatgg aaatcacatg tttgcaggac atctcaagtg caaagtccgt
1800atggagaaat tgagaatcaa gggaatgtca tacacgatgt gttcaggaaa gttctcaatt
1860gacaaagaga tggcagaaac acagcatggg acaacagtgg tgaaagtcaa gtatgaaggt
1920gctggagctc cgtgtaaagt ccccatagag ataagagatg tgaacaagga aaaagtggtt
1980gggcgtatca tctcatccac ccctttggct gagaatacca acagtgtaac caacatagag
2040ttagaacccc cctttgggga cagctacata gtgataggtg ttggaaacag tgcattaaca
2100ctccattggt tcaggaaagg gagttccatt ggcaagatgt ttgagtccac atacagaggt
2160gcaaaacgaa tggccattct aggtgaaaca gcttgggatt ttggttccgt tggtggactg
2220ttcacatcat tgggaaaggc tgtgcaccag gtttttggaa gtgtgtatac aaccctgttt
2280ggaggagtct catggatgat tagaatccta attgggttcc tagtgttgtg gattggcacg
2340aactcaagga acacttcaat ggctatgacg tgcatagctg ccggcattgt gacactgtat
2400ttgggagtca tggtgcaggc cgatagtggt tgcgttgtga gctggaaaaa caaagaactg
2460aaatgtggca gtgggatttt catcacagac aacgtgcaca catggacaga acaatacaag
2520ttccaaccag aatccccttc aaaactagct tcagctatcc agaaagccca tgaagaggac
2580atttgtggaa tccgctcagt aacaagactg gagaatctga tgtggaaaca aataacacca
2640gaattgaatc acattctatc agaaaatgag gtgaagttaa ctattatgac aggagacatc
2700aaaggaatca tgcaggcagg aaaacgatct ctgcggcctc agcccactga gctgaagtat
2760tcatggaaaa catggggcaa agcaaaaatg ctctctacag agtctcataa ccagaccttt
2820ctcattgatg gccccgaaac agcagaatgc cccaacacaa atagagcttg gaattcgttg
2880gaagttgaag actatggctt tggagtattc accaccaata tatggctaaa attgaaagaa
2940aaacaggatg tattctgcga ctcaaaactc atgtcagcgg ccataaaaga caacagagcc
3000gtccatgccg atatgggtta ttggatagaa agtgcactca atgacacatg gaagatagag
3060aaagcctctt tcattgaagt taaaaactgc cactggccaa aatcacacac cctctggagc
3120aatggagtgc tagaaagtga gatgataatt ccaaagaatc tcgctggacc agtgtctcaa
3180cacaactata gaccaggcta ccatacacaa ataacaggac catggcatct aggtaagctt
3240gagatggact ttgatttctg tgatggaaca acagtggtag tgactgagga ctgcggaaat
3300agaggaccct ctttgagaac aaccactgcc tctggaaaac tcataacaga atggtgctgc
3360cgatcttgca cattaccacc gctaagatac agaggtgagg atgggtgctg gtacgggatg
3420gaaatcagac cattgaagga gaaagaagag aatttggtca actccttggt cacagctgga
3480catgggcagg tcgacaactt ttcactagga gtcttgggaa tggcattgtt cctggaggaa
3540atgcttagga cccgagtagg aacgaaacat gcaatactac tagttgcagt ttcttttgtg
3600acattgatca cagggaacat gtcctttaga gacctgggaa gagtgatggt tatggtaggc
3660gccactatga cggatgacat aggtatgggc gtgacttatc ttgccctact agcagccttc
3720aaagtcagac caacttttgc agctggacta ctcttgagaa agctgacctc caaggaattg
3780atgatgacta ctataggaat tgtactcctc tcccagagca ccataccaga gaccattctt
3840gagttgactg atgcgttagc cttaggcatg atggtcctca aaatggtgag aaatatggaa
3900aagtatcaat tggcagtgac tatcatggct atcttgtgcg tcccaaacgc agtgatatta
3960caaaacgcat ggaaagtgag ttgcacaata ttggcagtgg tgtccgtttc cccactgttc
4020ttaacatcct cacagcaaaa aacagattgg ataccattag cattgacgat caaaggtctc
4080aatccaacag ctatttttct aacaaccctc tcaagaacca gcaagaaaag gagctggcca
4140ttaaatgagg ctatcatggc agtcgggatg gtgagcattt tagccagttc tctcctaaaa
4200aatgatattc ccatgacagg accattagtg gctggagggc tcctcactgt gtgctacgtg
4260ctcactggac gatcggccga tttggaactg gagagagcag ccgatgtcaa atgggaagac
4320caggcagaga tatcaggaag cagtccaatc ctgtcaataa caatatcaga agatggtagc
4380atgtcgataa aaaatgaaga ggaagaacaa acactgacca tactcattag aacaggattg
4440ctggtgatct caggactttt tcctgtatca ataccaatca cggcagcagc atggtacctg
4500tgggaagtga agaaacaacg ggccggagta ttgtgggatg ttccttcacc cccacccatg
4560ggaaaggctg aactggaaga tggagcctat agaattaagc aaaaagggat tcttggatat
4620tcccagatcg gagccggagt ttacaaagaa ggaacattcc atacaatgtg gcatgtcaca
4680cgtggcgctg ttctaatgca taaaggaaag aggattgaac catcatgggc ggacgtcaag
4740aaagacctaa tatcatatgg aggaggctgg aagttagaag gagaatggaa ggaaggagaa
4800gaagtccagg tattggcact ggagcctgga aaaaatccaa gagccgtcca aacgaaacct
4860ggtcttttca aaaccaacgc cggaacaata ggtgctgtat ctctggactt ttctcctgga
4920acgtcaggat ctccaattat cgacaaaaaa ggaaaagttg tgggtcttta tggtaatggt
4980gttgttacaa ggagtggagc atatgtgagt gctatagccc agactgaaaa aagcattgaa
5040gacaacccag agatcgaaga tgacattttc cgaaagagaa gactgaccat catggacctc
5100cacccaggag cgggaaagac gaagagatac cttccggcca tagtcagaga agctataaaa
5160cggggtttga gaacattaat cttggccccc actagagttg tggcagctga aatggaggaa
5220gcccttagag gacttccaat aagataccag accccagcca tcagagctgt gcacaccggg
5280cgggagattg tggacctaat gtgtcatgcc acatttacca tgaggctgct atcaccagtt
5340agagtgccaa actacaacct gattatcatg gacgaagccc atttcacaga cccagcaagt
5400atagcagcta gaggatacat ctcaactcga gtggagatgg gtgaggcagc tgggattttt
5460atgacagcca ctcccccggg aagcagagac ccatttcctc agagcaatgc accaatcata
5520gatgaagaaa gagaaatccc tgaacgctcg tggaattccg gacatgaatg ggtcacggat
5580tttaaaggga agactgtttg gttcgttcca agtataaaag caggaaatga tatagcagct
5640tgcctgagga aaaatggaaa gaaagtgata caactcagta ggaagacctt tgattctgag
5700tatgtcaaga ctagaaccaa tgattgggac ttcgtggtta caactgacat ttcagaaatg
5760ggtgccaatt tcaaggctga gagggttata gaccccagac gctgcatgaa accagtcata
5820ctaacagatg gtgaagagcg ggtgattctg gcaggaccta tgccagtgac ccactctagt
5880gcagcacaaa gaagagggag aataggaaga aatccaaaaa atgagaatga ccagtacata
5940tacatggggg aacctctgga aaatgatgaa gactgtgcac actggaaaga agctaaaatg
6000ctcctagata acatcaacac gccagaagga atcattccta gcatgttcga accagagcgt
6060gaaaaggtgg atgccattga tggcgaatac cgcttgagag gagaagcaag gaaaaccttt
6120gtagacttaa tgagaagagg agacctacca gtctggttgg cctacagagt ggcagctgaa
6180ggcatcaact acgcagacag aaggtggtgt tttgatggag tcaagaacaa ccaaatccta
6240gaagaaaacg tggaagttga aatctggaca aaagaagggg aaaggaagaa attgaaaccc
6300agatggttgg atgctaggat ctattctgac ccactggcgc taaaagaatt taaggaattt
6360gcagccggaa gaaagtctct gaccctgaac ctaatcacag aaatgggtag gctcccaacc
6420ttcatgactc agaaggcaag agacgcactg gacaacttag cagtgctgca cacggctgag
6480gcaggtggaa gggcgtacaa ccatgctctc agtgaactgc cggagaccct ggagacattg
6540cttttactga cacttctggc tacagtcacg ggagggatct ttttattctt gatgagcgca
6600aggggcatag ggaagatgac cctgggaatg tgctgcataa tcacggctag catcctccta
6660tggtacgcac aaatacagcc acactggata gcagcttcaa taatactgga gttttttctc
6720atagttttgc ttattccaga acctgaaaaa cagagaacac cccaagacaa ccaactgacc
6780tacgttgtca tagccatcct cacagtggtg gccgcaacca tggcaaacga gatgggtttc
6840ctagaaaaaa cgaagaaaga tctcggattg ggaagcattg caacccagca acccgagagc
6900aacatcctgg acatagatct acgtcctgca tcagcatgga cgctgtatgc cgtggccaca
6960acatttgtta caccaatgtt gagacatagc attgaaaatt cctcagtgaa tgtgtcccta
7020acagctatag ccaaccaagc cacagtgtta atgggtctcg ggaaaggatg gccattgtca
7080aagatggaca tcggagttcc ccttctcgcc attggatgct actcacaagt caaccccata
7140actctcacag cagctctttt cttattggta gcacattatg ccatcatagg gccaggactc
7200caagcaaaag caaccagaga agctcagaaa agagcagcgg cgggcatcat gaaaaaccca
7260actgtcgatg gaataacagt gattgaccta gatccaatac cttatgatcc aaagtttgaa
7320aagcagttgg gacaagtaat gctcctagtc ctctgcgtga ctcaagtatt gatgatgagg
7380actacatggg ctctgtgtga ggctttaacc ttagctaccg ggcccatctc cacattgtgg
7440gaaggaaatc cagggaggtt ttggaacact accattgcgg tgtcaatggc taacattttt
7500agagggagtt acttggccgg agctggactt ctcttttcta ttatgaagaa cacaaccaac
7560acaagaaggg gaactggcaa cataggagag acgcttggag agaaatggaa aagccgattg
7620aacgcattgg gaaaaagtga attccagatc tacaagaaaa gtggaatcca ggaagtggat
7680agaaccttag caaaagaagg cattaaaaga ggagaaacgg accatcacgc tgtgtcgcga
7740ggctcagcaa aactgagatg gttcgttgag agaaacatgg tcacaccaga agggaaagta
7800gtggacctcg gttgtggcag aggaggctgg tcatactatt gtggaggact aaagaatgta
7860agagaagtca aaggcctaac aaaaggagga ccaggacacg aagaacccat ccccatgtca
7920acatatgggt ggaatctagt gcgtcttcaa agtggagttg acgttttctt catcccgcca
7980gaaaagtgtg acacattatt gtgtgacata ggggagtcat caccaaatcc cacagtggaa
8040gcaggacgaa cactcagagt ccttaactta gtagaaaatt ggttgaacaa caacactcaa
8100ttttgcataa aggttctcaa cccatatatg ccctcagtca tagaaaaaat ggaagcacta
8160caaaggaaat atggaggagc cttagtgagg aatccactct cacgaaactc cacacatgag
8220atgtactggg tatccaatgc ttccgggaac atagtgtcat cagtgaacat gatttcaagg
8280atgttgatca acagatttac aatgagatac aagaaagcca cttacgagcc ggatgttgac
8340ctcggaagcg gaacccgtaa catcgggatt gaaagtgaga taccaaacct agatataatt
8400gggaaaagaa tagaaaaaat aaagcaagag catgaaacat catggcacta tgaccaagac
8460cacccataca aaacgtgggc ataccatggt agctatgaaa caaaacagac tggatcagca
8520tcatccatgg tcaacggagt ggtcaggctg ctgacaaaac cttgggacgt cgtccccatg
8580gtgacacaga tggcaatgac agacacgact ccatttggac aacagcgcgt ttttaaagag
8640aaagtggaca cgagaaccca agaaccgaaa gaaggcacga agaaactaat gaaaataaca
8700gcagagtggc tttggaaaga attagggaag aaaaagacac ccaggatgtg caccagagaa
8760gaattcacaa gaaaggtgag aagcaatgca gccttggggg ccatattcac tgatgagaac
8820aagtggaagt cggcacgtga ggctgttgaa gatagtaggt tttgggagct ggttgacaag
8880gaaaggaatc tccatcttga aggaaagtgt gaaacatgtg tgtacaacat gatgggaaaa
8940agagagaaga agctagggga attcggcaag gcaaaaggca gcagagccat atggtacatg
9000tggcttggag cacgcttctt agagtttgaa gccctaggat tcttaaatga agatcactgg
9060ttctccagag agaactccct gagtggagtg gaaggagaag ggctgcacaa gctaggttac
9120attctaagag acgtgagcaa gaaagaggga ggagcaatgt atgccgatga caccgcagga
9180tgggatacaa gaatcacact agaagaccta aaaaatgaag aaatggtaac aaaccacatg
9240gaaggagaac acaagaaact agccgaggcc attttcaaac taacgtacca aaacaaggtg
9300gtgcgtgtgc aaagaccaac accaagaggc acagtaatgg acatcatatc gagaagagac
9360caaagaggta gtggacaagt tggcacctat ggactcaata ctttcaccaa tatggaagcc
9420caactaatca gacagatgga gggagaagga gtctttaaaa gcattcagca cctaacaatc
9480acagaagaaa tcgctgtgca aaactggtta gcaagagtgg ggcgcgaaag gttatcaaga
9540atggccatca gtggagatga ttgtgttgtg aaacctttag atgacaggtt cgcaagcgct
9600ttaacagctc taaatgacat gggaaagatt aggaaagaca tacaacaatg ggaaccttca
9660agaggatgga atgattggac acaagtgccc ttctgttcac accatttcca tgagttaatc
9720atgaaagacg gtcgcgtact cgttgttcca tgtagaaacc aagatgaact gattggcaga
9780gcccgaatct cccaaggagc agggtggtct ttgcgggaga cggcctgttt ggggaagtct
9840tacgcccaaa tgtggagctt gatgtacttc cacagacgcg acctcaggct ggcggcaaat
9900gctatttgct cggcagtacc atcacattgg gttccaacaa gtcgaacaac ctggtccata
9960catgctaaac atgaatggat gacaacggaa gacatgctga cagtctggaa cagggtgtgg
10020attcaagaaa acccatggat ggaagacaaa actccagtgg aatcatggga ggaaatccca
10080tacttgggga aaagagaaga ccaatggtgc ggctcattga ttgggttaac aagcagggcc
10140acctgggcaa agaacatcca agcagcaata aatcaagtta gatcccttat aggcaatgaa
10200gaatacacag attacatgcc atccatgaaa agattcagaa gagaagagga agaagcagga
10260gttctgtggt agaaagcaaa actaacatga aacaaggcta gaagtcaggt cggattaagc
10320catagtacgg aaaaaactat gctacctgtg agccccgtcc aaggacgtta aaagaagtca
10380ggccatcata aatgccatag cttgagtaaa ctatgcagcc tgtagctcca cctgagaagg
10440tgtaaaaaat ccgggaggcc acaaaccatg gaagctgtac gcatggcgta gtggactagc
10500ggttagagga gacccctccc ttacaaatcg cagcaacaat gggggcccaa ggcgagatga
10560agctgtagtc tcgctggaag gactagaggt tagaggagac ccccccgaaa caaaaaacag
10620catattgacg ctgggaaaga ccagagatcc tgctgtctcc tcagcatcat tccaggcaca
10680gaacgccaga aaatggaatg gtgctgttga atcaacaggt tct
10723333391PRTArtificial SequenceDerived from Dengue virus serotype
2/Dengue virus serotype 4, DenVax-4j 33Met Asn Asn Gln Arg Lys Lys
Ala Lys Asn Thr Pro Phe Asn Met Leu 1 5
10 15 Lys Arg Glu Arg Asn Arg Val Ser Thr Val Gln
Gln Leu Thr Lys Arg 20 25
30 Phe Ser Leu Gly Met Leu Gln Gly Arg Gly Pro Leu Lys Leu Phe
Met 35 40 45 Ala
Leu Val Ala Phe Leu Arg Phe Leu Thr Ile Pro Pro Thr Ala Gly 50
55 60 Ile Leu Lys Arg Trp Gly
Thr Ile Lys Lys Ser Lys Ala Ile Asn Val 65 70
75 80 Leu Arg Gly Phe Arg Lys Glu Ile Gly Arg Met
Leu Asn Ile Leu Asn 85 90
95 Arg Arg Arg Ser Ser Ala Gly Met Ile Ile Met Leu Ile Pro Thr Val
100 105 110 Met Ala
Phe His Leu Thr Thr Arg Asp Gly Glu Pro Leu Met Ile Val 115
120 125 Ala Lys His Glu Arg Gly Arg
Pro Leu Leu Phe Lys Thr Thr Glu Gly 130 135
140 Ile Asn Lys Cys Thr Leu Ile Ala Met Asp Leu Gly
Glu Met Cys Glu 145 150 155
160 Asp Thr Val Thr Tyr Lys Cys Pro Leu Leu Val Asn Thr Glu Pro Glu
165 170 175 Asp Ile Asp
Cys Trp Cys Asn Leu Thr Ser Thr Trp Val Met Tyr Gly 180
185 190 Thr Cys Thr Gln Ser Gly Glu Arg
Arg Arg Glu Lys Arg Ser Val Ala 195 200
205 Leu Thr Pro His Ser Gly Met Gly Leu Glu Thr Arg Ala
Glu Thr Trp 210 215 220
Met Ser Ser Glu Gly Ala Trp Lys His Ala Gln Arg Val Glu Ser Trp 225
230 235 240 Ile Leu Arg Asn
Pro Gly Phe Ala Leu Leu Ala Gly Phe Met Ala Tyr 245
250 255 Met Ile Gly Gln Thr Gly Ile Gln Arg
Thr Val Phe Phe Val Leu Met 260 265
270 Met Leu Val Ala Pro Ser Tyr Gly Met Arg Cys Val Gly Val
Gly Asn 275 280 285
Arg Asp Phe Val Glu Gly Val Ser Gly Gly Ala Trp Val Asp Leu Val 290
295 300 Leu Glu His Gly Gly
Cys Val Thr Thr Met Ala Gln Gly Lys Pro Thr 305 310
315 320 Leu Asp Phe Glu Leu Thr Lys Thr Thr Ala
Lys Glu Val Ala Leu Leu 325 330
335 Arg Thr Tyr Cys Ile Glu Ala Ser Ile Ser Asn Ile Thr Thr Ala
Thr 340 345 350 Arg
Cys Pro Thr Gln Gly Glu Pro Tyr Leu Lys Glu Glu Gln Asp Gln 355
360 365 Gln Tyr Ile Cys Arg Arg
Asp Val Val Asp Arg Gly Trp Gly Asn Gly 370 375
380 Cys Gly Leu Phe Gly Lys Gly Gly Val Val Thr
Cys Ala Lys Phe Ser 385 390 395
400 Cys Ser Gly Lys Ile Thr Gly Asn Leu Val Gln Ile Glu Asn Leu Glu
405 410 415 Tyr Thr
Val Val Val Thr Val His Asn Gly Asp Thr His Ala Val Gly 420
425 430 Asn Asp Thr Ser Asn His Gly
Val Thr Ala Thr Ile Thr Pro Arg Ser 435 440
445 Pro Ser Val Glu Val Lys Leu Pro Asp Tyr Gly Glu
Leu Thr Leu Asp 450 455 460
Cys Glu Pro Arg Ser Gly Ile Asp Phe Asn Glu Met Ile Leu Met Lys 465
470 475 480 Met Lys Lys
Lys Thr Trp Leu Val His Lys Gln Trp Phe Leu Asp Leu 485
490 495 Pro Leu Pro Trp Thr Ala Gly Ala
Asp Thr Ser Glu Val His Trp Asn 500 505
510 Tyr Lys Glu Arg Met Val Thr Phe Lys Val Pro His Ala
Lys Arg Gln 515 520 525
Asp Val Thr Val Leu Gly Ser Gln Glu Gly Ala Met His Ser Ala Leu 530
535 540 Ala Gly Ala Thr
Glu Val Asp Ser Gly Asp Gly Asn His Met Phe Ala 545 550
555 560 Gly His Leu Lys Cys Lys Val Arg Met
Glu Lys Leu Arg Ile Lys Gly 565 570
575 Met Ser Tyr Thr Met Cys Ser Gly Lys Phe Ser Ile Asp Lys
Glu Met 580 585 590
Ala Glu Thr Gln His Gly Thr Thr Val Val Lys Val Lys Tyr Glu Gly
595 600 605 Ala Gly Ala Pro
Cys Lys Val Pro Ile Glu Ile Arg Asp Val Asn Lys 610
615 620 Glu Lys Val Val Gly Arg Ile Ile
Ser Ser Thr Pro Leu Ala Glu Asn 625 630
635 640 Thr Asn Ser Val Thr Asn Ile Glu Leu Glu Pro Pro
Phe Gly Asp Ser 645 650
655 Tyr Ile Val Ile Gly Val Gly Asn Ser Ala Leu Thr Leu His Trp Phe
660 665 670 Arg Lys Gly
Ser Ser Ile Gly Lys Met Phe Glu Ser Thr Tyr Arg Gly 675
680 685 Ala Lys Arg Met Ala Ile Leu Gly
Glu Thr Ala Trp Asp Phe Gly Ser 690 695
700 Val Gly Gly Leu Phe Thr Ser Leu Gly Lys Ala Val His
Gln Val Phe 705 710 715
720 Gly Ser Val Tyr Thr Thr Leu Phe Gly Gly Val Ser Trp Met Ile Arg
725 730 735 Ile Leu Ile Gly
Phe Leu Val Leu Trp Ile Gly Thr Asn Ser Arg Asn 740
745 750 Thr Ser Met Ala Met Thr Cys Ile Ala
Ala Gly Ile Val Thr Leu Tyr 755 760
765 Leu Gly Val Met Val Gln Ala Asp Ser Gly Cys Val Val Ser
Trp Lys 770 775 780
Asn Lys Glu Leu Lys Cys Gly Ser Gly Ile Phe Ile Thr Asp Asn Val 785
790 795 800 His Thr Trp Thr Glu
Gln Tyr Lys Phe Gln Pro Glu Ser Pro Ser Lys 805
810 815 Leu Ala Ser Ala Ile Gln Lys Ala His Glu
Glu Asp Ile Cys Gly Ile 820 825
830 Arg Ser Val Thr Arg Leu Glu Asn Leu Met Trp Lys Gln Ile Thr
Pro 835 840 845 Glu
Leu Asn His Ile Leu Ser Glu Asn Glu Val Lys Leu Thr Ile Met 850
855 860 Thr Gly Asp Ile Lys Gly
Ile Met Gln Ala Gly Lys Arg Ser Leu Arg 865 870
875 880 Pro Gln Pro Thr Glu Leu Lys Tyr Ser Trp Lys
Thr Trp Gly Lys Ala 885 890
895 Lys Met Leu Ser Thr Glu Ser His Asn Gln Thr Phe Leu Ile Asp Gly
900 905 910 Pro Glu
Thr Ala Glu Cys Pro Asn Thr Asn Arg Ala Trp Asn Ser Leu 915
920 925 Glu Val Glu Asp Tyr Gly Phe
Gly Val Phe Thr Thr Asn Ile Trp Leu 930 935
940 Lys Leu Lys Glu Lys Gln Asp Val Phe Cys Asp Ser
Lys Leu Met Ser 945 950 955
960 Ala Ala Ile Lys Asp Asn Arg Ala Val His Ala Asp Met Gly Tyr Trp
965 970 975 Ile Glu Ser
Ala Leu Asn Asp Thr Trp Lys Ile Glu Lys Ala Ser Phe 980
985 990 Ile Glu Val Lys Asn Cys His Trp
Pro Lys Ser His Thr Leu Trp Ser 995 1000
1005 Asn Gly Val Leu Glu Ser Glu Met Ile Ile Pro
Lys Asn Leu Ala 1010 1015 1020
Gly Pro Val Ser Gln His Asn Tyr Arg Pro Gly Tyr His Thr Gln
1025 1030 1035 Ile Thr Gly
Pro Trp His Leu Gly Lys Leu Glu Met Asp Phe Asp 1040
1045 1050 Phe Cys Asp Gly Thr Thr Val Val
Val Thr Glu Asp Cys Gly Asn 1055 1060
1065 Arg Gly Pro Ser Leu Arg Thr Thr Thr Ala Ser Gly Lys
Leu Ile 1070 1075 1080
Thr Glu Trp Cys Cys Arg Ser Cys Thr Leu Pro Pro Leu Arg Tyr 1085
1090 1095 Arg Gly Glu Asp Gly
Cys Trp Tyr Gly Met Glu Ile Arg Pro Leu 1100 1105
1110 Lys Glu Lys Glu Glu Asn Leu Val Asn Ser
Leu Val Thr Ala Gly 1115 1120 1125
His Gly Gln Val Asp Asn Phe Ser Leu Gly Val Leu Gly Met Ala
1130 1135 1140 Leu Phe
Leu Glu Glu Met Leu Arg Thr Arg Val Gly Thr Lys His 1145
1150 1155 Ala Ile Leu Leu Val Ala Val
Ser Phe Val Thr Leu Ile Thr Gly 1160 1165
1170 Asn Met Ser Phe Arg Asp Leu Gly Arg Val Met Val
Met Val Gly 1175 1180 1185
Ala Thr Met Thr Asp Asp Ile Gly Met Gly Val Thr Tyr Leu Ala 1190
1195 1200 Leu Leu Ala Ala Phe
Lys Val Arg Pro Thr Phe Ala Ala Gly Leu 1205 1210
1215 Leu Leu Arg Lys Leu Thr Ser Lys Glu Leu
Met Met Thr Thr Ile 1220 1225 1230
Gly Ile Val Leu Leu Ser Gln Ser Thr Ile Pro Glu Thr Ile Leu
1235 1240 1245 Glu Leu
Thr Asp Ala Leu Ala Leu Gly Met Met Val Leu Lys Met 1250
1255 1260 Val Arg Asn Met Glu Lys Tyr
Gln Leu Ala Val Thr Ile Met Ala 1265 1270
1275 Ile Leu Cys Val Pro Asn Ala Val Ile Leu Gln Asn
Ala Trp Lys 1280 1285 1290
Val Ser Cys Thr Ile Leu Ala Val Val Ser Val Ser Pro Leu Phe 1295
1300 1305 Leu Thr Ser Ser Gln
Gln Lys Thr Asp Trp Ile Pro Leu Ala Leu 1310 1315
1320 Thr Ile Lys Gly Leu Asn Pro Thr Ala Ile
Phe Leu Thr Thr Leu 1325 1330 1335
Ser Arg Thr Ser Lys Lys Arg Ser Trp Pro Leu Asn Glu Ala Ile
1340 1345 1350 Met Ala
Val Gly Met Val Ser Ile Leu Ala Ser Ser Leu Leu Lys 1355
1360 1365 Asn Asp Ile Pro Met Thr Gly
Pro Leu Val Ala Gly Gly Leu Leu 1370 1375
1380 Thr Val Cys Tyr Val Leu Thr Gly Arg Ser Ala Asp
Leu Glu Leu 1385 1390 1395
Glu Arg Ala Ala Asp Val Lys Trp Glu Asp Gln Ala Glu Ile Ser 1400
1405 1410 Gly Ser Ser Pro Ile
Leu Ser Ile Thr Ile Ser Glu Asp Gly Ser 1415 1420
1425 Met Ser Ile Lys Asn Glu Glu Glu Glu Gln
Thr Leu Thr Ile Leu 1430 1435 1440
Ile Arg Thr Gly Leu Leu Val Ile Ser Gly Leu Phe Pro Val Ser
1445 1450 1455 Ile Pro
Ile Thr Ala Ala Ala Trp Tyr Leu Trp Glu Val Lys Lys 1460
1465 1470 Gln Arg Ala Gly Val Leu Trp
Asp Val Pro Ser Pro Pro Pro Met 1475 1480
1485 Gly Lys Ala Glu Leu Glu Asp Gly Ala Tyr Arg Ile
Lys Gln Lys 1490 1495 1500
Gly Ile Leu Gly Tyr Ser Gln Ile Gly Ala Gly Val Tyr Lys Glu 1505
1510 1515 Gly Thr Phe His Thr
Met Trp His Val Thr Arg Gly Ala Val Leu 1520 1525
1530 Met His Lys Gly Lys Arg Ile Glu Pro Ser
Trp Ala Asp Val Lys 1535 1540 1545
Lys Asp Leu Ile Ser Tyr Gly Gly Gly Trp Lys Leu Glu Gly Glu
1550 1555 1560 Trp Lys
Glu Gly Glu Glu Val Gln Val Leu Ala Leu Glu Pro Gly 1565
1570 1575 Lys Asn Pro Arg Ala Val Gln
Thr Lys Pro Gly Leu Phe Lys Thr 1580 1585
1590 Asn Ala Gly Thr Ile Gly Ala Val Ser Leu Asp Phe
Ser Pro Gly 1595 1600 1605
Thr Ser Gly Ser Pro Ile Ile Asp Lys Lys Gly Lys Val Val Gly 1610
1615 1620 Leu Tyr Gly Asn Gly
Val Val Thr Arg Ser Gly Ala Tyr Val Ser 1625 1630
1635 Ala Ile Ala Gln Thr Glu Lys Ser Ile Glu
Asp Asn Pro Glu Ile 1640 1645 1650
Glu Asp Asp Ile Phe Arg Lys Arg Arg Leu Thr Ile Met Asp Leu
1655 1660 1665 His Pro
Gly Ala Gly Lys Thr Lys Arg Tyr Leu Pro Ala Ile Val 1670
1675 1680 Arg Glu Ala Ile Lys Arg Gly
Leu Arg Thr Leu Ile Leu Ala Pro 1685 1690
1695 Thr Arg Val Val Ala Ala Glu Met Glu Glu Ala Leu
Arg Gly Leu 1700 1705 1710
Pro Ile Arg Tyr Gln Thr Pro Ala Ile Arg Ala Val His Thr Gly 1715
1720 1725 Arg Glu Ile Val Asp
Leu Met Cys His Ala Thr Phe Thr Met Arg 1730 1735
1740 Leu Leu Ser Pro Val Arg Val Pro Asn Tyr
Asn Leu Ile Ile Met 1745 1750 1755
Asp Glu Ala His Phe Thr Asp Pro Ala Ser Ile Ala Ala Arg Gly
1760 1765 1770 Tyr Ile
Ser Thr Arg Val Glu Met Gly Glu Ala Ala Gly Ile Phe 1775
1780 1785 Met Thr Ala Thr Pro Pro Gly
Ser Arg Asp Pro Phe Pro Gln Ser 1790 1795
1800 Asn Ala Pro Ile Ile Asp Glu Glu Arg Glu Ile Pro
Glu Arg Ser 1805 1810 1815
Trp Asn Ser Gly His Glu Trp Val Thr Asp Phe Lys Gly Lys Thr 1820
1825 1830 Val Trp Phe Val Pro
Ser Ile Lys Ala Gly Asn Asp Ile Ala Ala 1835 1840
1845 Cys Leu Arg Lys Asn Gly Lys Lys Val Ile
Gln Leu Ser Arg Lys 1850 1855 1860
Thr Phe Asp Ser Glu Tyr Val Lys Thr Arg Thr Asn Asp Trp Asp
1865 1870 1875 Phe Val
Val Thr Thr Asp Ile Ser Glu Met Gly Ala Asn Phe Lys 1880
1885 1890 Ala Glu Arg Val Ile Asp Pro
Arg Arg Cys Met Lys Pro Val Ile 1895 1900
1905 Leu Thr Asp Gly Glu Glu Arg Val Ile Leu Ala Gly
Pro Met Pro 1910 1915 1920
Val Thr His Ser Ser Ala Ala Gln Arg Arg Gly Arg Ile Gly Arg 1925
1930 1935 Asn Pro Lys Asn Glu
Asn Asp Gln Tyr Ile Tyr Met Gly Glu Pro 1940 1945
1950 Leu Glu Asn Asp Glu Asp Cys Ala His Trp
Lys Glu Ala Lys Met 1955 1960 1965
Leu Leu Asp Asn Ile Asn Thr Pro Glu Gly Ile Ile Pro Ser Met
1970 1975 1980 Phe Glu
Pro Glu Arg Glu Lys Val Asp Ala Ile Asp Gly Glu Tyr 1985
1990 1995 Arg Leu Arg Gly Glu Ala Arg
Lys Thr Phe Val Asp Leu Met Arg 2000 2005
2010 Arg Gly Asp Leu Pro Val Trp Leu Ala Tyr Arg Val
Ala Ala Glu 2015 2020 2025
Gly Ile Asn Tyr Ala Asp Arg Arg Trp Cys Phe Asp Gly Val Lys 2030
2035 2040 Asn Asn Gln Ile Leu
Glu Glu Asn Val Glu Val Glu Ile Trp Thr 2045 2050
2055 Lys Glu Gly Glu Arg Lys Lys Leu Lys Pro
Arg Trp Leu Asp Ala 2060 2065 2070
Arg Ile Tyr Ser Asp Pro Leu Ala Leu Lys Glu Phe Lys Glu Phe
2075 2080 2085 Ala Ala
Gly Arg Lys Ser Leu Thr Leu Asn Leu Ile Thr Glu Met 2090
2095 2100 Gly Arg Leu Pro Thr Phe Met
Thr Gln Lys Ala Arg Asp Ala Leu 2105 2110
2115 Asp Asn Leu Ala Val Leu His Thr Ala Glu Ala Gly
Gly Arg Ala 2120 2125 2130
Tyr Asn His Ala Leu Ser Glu Leu Pro Glu Thr Leu Glu Thr Leu 2135
2140 2145 Leu Leu Leu Thr Leu
Leu Ala Thr Val Thr Gly Gly Ile Phe Leu 2150 2155
2160 Phe Leu Met Ser Ala Arg Gly Ile Gly Lys
Met Thr Leu Gly Met 2165 2170 2175
Cys Cys Ile Ile Thr Ala Ser Ile Leu Leu Trp Tyr Ala Gln Ile
2180 2185 2190 Gln Pro
His Trp Ile Ala Ala Ser Ile Ile Leu Glu Phe Phe Leu 2195
2200 2205 Ile Val Leu Leu Ile Pro Glu
Pro Glu Lys Gln Arg Thr Pro Gln 2210 2215
2220 Asp Asn Gln Leu Thr Tyr Val Val Ile Ala Ile Leu
Thr Val Val 2225 2230 2235
Ala Ala Thr Met Ala Asn Glu Met Gly Phe Leu Glu Lys Thr Lys 2240
2245 2250 Lys Asp Leu Gly Leu
Gly Ser Ile Ala Thr Gln Gln Pro Glu Ser 2255 2260
2265 Asn Ile Leu Asp Ile Asp Leu Arg Pro Ala
Ser Ala Trp Thr Leu 2270 2275 2280
Tyr Ala Val Ala Thr Thr Phe Val Thr Pro Met Leu Arg His Ser
2285 2290 2295 Ile Glu
Asn Ser Ser Val Asn Val Ser Leu Thr Ala Ile Ala Asn 2300
2305 2310 Gln Ala Thr Val Leu Met Gly
Leu Gly Lys Gly Trp Pro Leu Ser 2315 2320
2325 Lys Met Asp Ile Gly Val Pro Leu Leu Ala Ile Gly
Cys Tyr Ser 2330 2335 2340
Gln Val Asn Pro Ile Thr Leu Thr Ala Ala Leu Phe Leu Leu Val 2345
2350 2355 Ala His Tyr Ala Ile
Ile Gly Pro Gly Leu Gln Ala Lys Ala Thr 2360 2365
2370 Arg Glu Ala Gln Lys Arg Ala Ala Ala Gly
Ile Met Lys Asn Pro 2375 2380 2385
Thr Val Asp Gly Ile Thr Val Ile Asp Leu Asp Pro Ile Pro Tyr
2390 2395 2400 Asp Pro
Lys Phe Glu Lys Gln Leu Gly Gln Val Met Leu Leu Val 2405
2410 2415 Leu Cys Val Thr Gln Val Leu
Met Met Arg Thr Thr Trp Ala Leu 2420 2425
2430 Cys Glu Ala Leu Thr Leu Ala Thr Gly Pro Ile Ser
Thr Leu Trp 2435 2440 2445
Glu Gly Asn Pro Gly Arg Phe Trp Asn Thr Thr Ile Ala Val Ser 2450
2455 2460 Met Ala Asn Ile Phe
Arg Gly Ser Tyr Leu Ala Gly Ala Gly Leu 2465 2470
2475 Leu Phe Ser Ile Met Lys Asn Thr Thr Asn
Thr Arg Arg Gly Thr 2480 2485 2490
Gly Asn Ile Gly Glu Thr Leu Gly Glu Lys Trp Lys Ser Arg Leu
2495 2500 2505 Asn Ala
Leu Gly Lys Ser Glu Phe Gln Ile Tyr Lys Lys Ser Gly 2510
2515 2520 Ile Gln Glu Val Asp Arg Thr
Leu Ala Lys Glu Gly Ile Lys Arg 2525 2530
2535 Gly Glu Thr Asp His His Ala Val Ser Arg Gly Ser
Ala Lys Leu 2540 2545 2550
Arg Trp Phe Val Glu Arg Asn Met Val Thr Pro Glu Gly Lys Val 2555
2560 2565 Val Asp Leu Gly Cys
Gly Arg Gly Gly Trp Ser Tyr Tyr Cys Gly 2570 2575
2580 Gly Leu Lys Asn Val Arg Glu Val Lys Gly
Leu Thr Lys Gly Gly 2585 2590 2595
Pro Gly His Glu Glu Pro Ile Pro Met Ser Thr Tyr Gly Trp Asn
2600 2605 2610 Leu Val
Arg Leu Gln Ser Gly Val Asp Val Phe Phe Ile Pro Pro 2615
2620 2625 Glu Lys Cys Asp Thr Leu Leu
Cys Asp Ile Gly Glu Ser Ser Pro 2630 2635
2640 Asn Pro Thr Val Glu Ala Gly Arg Thr Leu Arg Val
Leu Asn Leu 2645 2650 2655
Val Glu Asn Trp Leu Asn Asn Asn Thr Gln Phe Cys Ile Lys Val 2660
2665 2670 Leu Asn Pro Tyr Met
Pro Ser Val Ile Glu Lys Met Glu Ala Leu 2675 2680
2685 Gln Arg Lys Tyr Gly Gly Ala Leu Val Arg
Asn Pro Leu Ser Arg 2690 2695 2700
Asn Ser Thr His Glu Met Tyr Trp Val Ser Asn Ala Ser Gly Asn
2705 2710 2715 Ile Val
Ser Ser Val Asn Met Ile Ser Arg Met Leu Ile Asn Arg 2720
2725 2730 Phe Thr Met Arg Tyr Lys Lys
Ala Thr Tyr Glu Pro Asp Val Asp 2735 2740
2745 Leu Gly Ser Gly Thr Arg Asn Ile Gly Ile Glu Ser
Glu Ile Pro 2750 2755 2760
Asn Leu Asp Ile Ile Gly Lys Arg Ile Glu Lys Ile Lys Gln Glu 2765
2770 2775 His Glu Thr Ser Trp
His Tyr Asp Gln Asp His Pro Tyr Lys Thr 2780 2785
2790 Trp Ala Tyr His Gly Ser Tyr Glu Thr Lys
Gln Thr Gly Ser Ala 2795 2800 2805
Ser Ser Met Val Asn Gly Val Val Arg Leu Leu Thr Lys Pro Trp
2810 2815 2820 Asp Val
Val Pro Met Val Thr Gln Met Ala Met Thr Asp Thr Thr 2825
2830 2835 Pro Phe Gly Gln Gln Arg Val
Phe Lys Glu Lys Val Asp Thr Arg 2840 2845
2850 Thr Gln Glu Pro Lys Glu Gly Thr Lys Lys Leu Met
Lys Ile Thr 2855 2860 2865
Ala Glu Trp Leu Trp Lys Glu Leu Gly Lys Lys Lys Thr Pro Arg 2870
2875 2880 Met Cys Thr Arg Glu
Glu Phe Thr Arg Lys Val Arg Ser Asn Ala 2885 2890
2895 Ala Leu Gly Ala Ile Phe Thr Asp Glu Asn
Lys Trp Lys Ser Ala 2900 2905 2910
Arg Glu Ala Val Glu Asp Ser Arg Phe Trp Glu Leu Val Asp Lys
2915 2920 2925 Glu Arg
Asn Leu His Leu Glu Gly Lys Cys Glu Thr Cys Val Tyr 2930
2935 2940 Asn Met Met Gly Lys Arg Glu
Lys Lys Leu Gly Glu Phe Gly Lys 2945 2950
2955 Ala Lys Gly Ser Arg Ala Ile Trp Tyr Met Trp Leu
Gly Ala Arg 2960 2965 2970
Phe Leu Glu Phe Glu Ala Leu Gly Phe Leu Asn Glu Asp His Trp 2975
2980 2985 Phe Ser Arg Glu Asn
Ser Leu Ser Gly Val Glu Gly Glu Gly Leu 2990 2995
3000 His Lys Leu Gly Tyr Ile Leu Arg Asp Val
Ser Lys Lys Glu Gly 3005 3010 3015
Gly Ala Met Tyr Ala Asp Asp Thr Ala Gly Trp Asp Thr Arg Ile
3020 3025 3030 Thr Leu
Glu Asp Leu Lys Asn Glu Glu Met Val Thr Asn His Met 3035
3040 3045 Glu Gly Glu His Lys Lys Leu
Ala Glu Ala Ile Phe Lys Leu Thr 3050 3055
3060 Tyr Gln Asn Lys Val Val Arg Val Gln Arg Pro Thr
Pro Arg Gly 3065 3070 3075
Thr Val Met Asp Ile Ile Ser Arg Arg Asp Gln Arg Gly Ser Gly 3080
3085 3090 Gln Val Gly Thr Tyr
Gly Leu Asn Thr Phe Thr Asn Met Glu Ala 3095 3100
3105 Gln Leu Ile Arg Gln Met Glu Gly Glu Gly
Val Phe Lys Ser Ile 3110 3115 3120
Gln His Leu Thr Ile Thr Glu Glu Ile Ala Val Gln Asn Trp Leu
3125 3130 3135 Ala Arg
Val Gly Arg Glu Arg Leu Ser Arg Met Ala Ile Ser Gly 3140
3145 3150 Asp Asp Cys Val Val Lys Pro
Leu Asp Asp Arg Phe Ala Ser Ala 3155 3160
3165 Leu Thr Ala Leu Asn Asp Met Gly Lys Ile Arg Lys
Asp Ile Gln 3170 3175 3180
Gln Trp Glu Pro Ser Arg Gly Trp Asn Asp Trp Thr Gln Val Pro 3185
3190 3195 Phe Cys Ser His His
Phe His Glu Leu Ile Met Lys Asp Gly Arg 3200 3205
3210 Val Leu Val Val Pro Cys Arg Asn Gln Asp
Glu Leu Ile Gly Arg 3215 3220 3225
Ala Arg Ile Ser Gln Gly Ala Gly Trp Ser Leu Arg Glu Thr Ala
3230 3235 3240 Cys Leu
Gly Lys Ser Tyr Ala Gln Met Trp Ser Leu Met Tyr Phe 3245
3250 3255 His Arg Arg Asp Leu Arg Leu
Ala Ala Asn Ala Ile Cys Ser Ala 3260 3265
3270 Val Pro Ser His Trp Val Pro Thr Ser Arg Thr Thr
Trp Ser Ile 3275 3280 3285
His Ala Lys His Glu Trp Met Thr Thr Glu Asp Met Leu Thr Val 3290
3295 3300 Trp Asn Arg Val Trp
Ile Gln Glu Asn Pro Trp Met Glu Asp Lys 3305 3310
3315 Thr Pro Val Glu Ser Trp Glu Glu Ile Pro
Tyr Leu Gly Lys Arg 3320 3325 3330
Glu Asp Gln Trp Cys Gly Ser Leu Ile Gly Leu Thr Ser Arg Ala
3335 3340 3345 Thr Trp
Ala Lys Asn Ile Gln Ala Ala Ile Asn Gln Val Arg Ser 3350
3355 3360 Leu Ile Gly Asn Glu Glu Tyr
Thr Asp Tyr Met Pro Ser Met Lys 3365 3370
3375 Arg Phe Arg Arg Glu Glu Glu Glu Ala Gly Val Leu
Trp 3380 3385 3390
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