1887

Abstract

Dengue virus (DENV) is currently among the most important human pathogens and affects millions of people throughout the tropical and subtropical regions of the world. Although it has been a World Health Organization priority for several years, there is still no efficient vaccine available to prevent infection. The envelope glycoprotein (E), exposed on the surface on infective viral particles, is the main target of neutralizing antibodies. For this reason it has been used as the antigen of choice for vaccine development efforts. Here we show a detailed analysis of factors involved in the expression, secretion and folding of E ectodomain from all four DENV serotypes in mammalian cells, and how this affects their ability to induce neutralizing antibody responses in DNA-vaccinated mice. Proper folding of E domain II (DII) is essential for efficient E ectodomain secretion, with DIII playing a significant role in stabilizing soluble dimers. We also show that the level of protein secreted from transfected cells determines the strength and efficiency of antibody responses in the context of DNA vaccination and should be considered a pivotal feature for the development of E-based DNA vaccines against DENV.

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2015-11-01
2024-10-03
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References

  1. Allison S.L., Schalich J., Stiasny K., Mandl C.W., Heinz F.X. 2001; Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J Virol 75:4268–4275 [View Article][PubMed]
    [Google Scholar]
  2. Apt D., Raviprakash K., Brinkman A., Semyonov A., Yang S., Skinner C., Diehl L., Lyons R., Porter K., Punnonen J. 2006; Tetravalent neutralizing antibody response against four dengue serotypes by a single chimeric dengue envelope antigen. Vaccine 24:335–344 [View Article][PubMed]
    [Google Scholar]
  3. Azevedo A.S., Yamamura A.M., Freire M.S., Trindade G.F., Bonaldo M., Galler R., Alves A.M. 2011; DNA vaccines against dengue virus type 2 based on truncate envelope protein or its domain III. PLoS One 6:e20528 [View Article][PubMed]
    [Google Scholar]
  4. Bäck A.T., Lundkvist A. 2013; Dengue viruses – an overview. Infect Ecol Epidemiol 3:19839
    [Google Scholar]
  5. Beckett D., Kovaleva E., Schatz P.J. 1999; A minimal peptide substrate in biotin holoenzyme synthetase-catalyzed biotinylation. Protein Sci 8:921–929 [CrossRef]
    [Google Scholar]
  6. Beckett C.G., Tjaden J., Burgess T., Danko J.R., Tamminga C., Simmons M., Wu S.J., Sun P., Kochel T., other authors. 2011; Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial. Vaccine 29:960–968 [View Article][PubMed]
    [Google Scholar]
  7. Benvenuti F., Burrone O.R. 2001; Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined V(L)/V(H) determinants. Gene Ther 8:1555–1561 [View Article][PubMed]
    [Google Scholar]
  8. Butrapet S., Childers T., Moss K.J., Erb S.M., Luy B.E., Calvert A.E., Blair C.D., Roehrig J.T., Huang C.Y. 2011; Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion. Virology 413:118–127 [View Article][PubMed]
    [Google Scholar]
  9. Cesco-Gaspere M., Benvenuti F., Burrone O.R. 2005; BCL1 lymphoma protection induced by idiotype DNA vaccination is entirely dependent on anti-idiotypic antibodies. Cancer Immunol Immunother 54:351–358 [View Article][PubMed]
    [Google Scholar]
  10. Coban C., Kobiyama K., Aoshi T., Takeshita F., Horii T., Akira S., Ishii K.J. 2011; Novel strategies to improve DNA vaccine immunogenicity. Curr Gene Ther 11:479–484 [View Article][PubMed]
    [Google Scholar]
  11. Coller B.A., Clements D.E., Bett A.J., Sagar S.L., Ter Meulen J.H. 2011; The development of recombinant subunit envelope-based vaccines to protect against dengue virus induced disease. Vaccine 29:7267–7275 [View Article][PubMed]
    [Google Scholar]
  12. Crill W.D., Roehrig J.T. 2001; Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J Virol 75:7769–7773 [View Article][PubMed]
    [Google Scholar]
  13. Danko J.R., Beckett C.G., Porter K.R. 2011; Development of dengue DNA vaccines. Vaccine 29:7261–7266 [View Article][PubMed]
    [Google Scholar]
  14. De Paula S.O., Lima D.M., de Oliveira França R.F., Gomes-Ruiz A.C., da Fonseca B.A. 2008; A DNA vaccine candidate expressing dengue-3 virus prM and E proteins elicits neutralizing antibodies and protects mice against lethal challenge. Arch Virol 153:2215–2223 [View Article][PubMed]
    [Google Scholar]
  15. de Souza V.A., Fernandes S., Araújo E.S., Tateno A.F., Oliveira O.M., Oliveira R.R., Pannuti C.S. 2004; Use of an immunoglobulin G avidity test to discriminate between primary and secondary dengue virus infections. J Clin Microbiol 42:1782–1784 [View Article][PubMed]
    [Google Scholar]
  16. de Wispelaere M., Yang P.L. 2012; Mutagenesis of the DI/DIII linker in dengue virus envelope protein impairs viral particle assembly. J Virol 86:7072–7083 [View Article][PubMed]
    [Google Scholar]
  17. Dejnirattisai W., Jumnainsong A., Onsirisakul N., Fitton P., Vasanawathana S., Limpitikul W., Puttikhunt C., Edwards C., Duangchinda T., other authors. 2010; Cross-reacting antibodies enhance dengue virus infection in humans. Science 328:745–748 [View Article][PubMed]
    [Google Scholar]
  18. Dejnirattisai W., Wongwiwat W., Supasa S., Zhang X., Dai X., Rouvinski A., Jumnainsong A., Edwards C., Quyen N.T., other authors. 2015; A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus. Nat Immunol 16:170–177 [View Article][PubMed]
    [Google Scholar]
  19. Erb S.M., Butrapet S., Moss K.J., Luy B.E., Childers T., Calvert A.E., Silengo S.J., Roehrig J.T., Huang C.Y., Blair C.D. 2010; Domain-III FG loop of the dengue virus type 2 envelope protein is important for infection of mammalian cells and Aedes aegypti mosquitoes. Virology 406:328–335 [View Article][PubMed]
    [Google Scholar]
  20. Galula J.U., Shen W.F., Chuang S.T., Chang G.J., Chao D.Y. 2014; Virus-like particle secretion and genotype-dependent immunogenicity of dengue virus serotype 2 DNA vaccine. J Virol 88:10813–10830 [View Article][PubMed]
    [Google Scholar]
  21. Ge P., Zhou Z.H. 2014; Chaperone fusion proteins aid entropy-driven maturation of class II viral fusion proteins. Trends Microbiol 22:100–106 [View Article][PubMed]
    [Google Scholar]
  22. Graham B.S., Koup R.A., Roederer M., Bailer R.T., Enama M.E., Moodie Z., Martin J.E., McCluskey M.M., Chakrabarti B.K., other authors. 2006; Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis 194:1650–1660 [View Article][PubMed]
    [Google Scholar]
  23. Gromowski G.D., Barrett N.D., Barrett A.D. 2008; Characterization of dengue virus complex-specific neutralizing epitopes on envelope protein domain III of dengue 2 virus. J Virol 82:8828–8837 [View Article][PubMed]
    [Google Scholar]
  24. Gulland A. 2013; Burden of dengue fever is higher than previously thought. BMJ 347:f6280 [View Article][PubMed]
    [Google Scholar]
  25. Guzmán M.G., Rodríguez R., Rodríguez R., Hermida L., Alvarez M., Lazo L., Muné M., Rosario D., Valdés K., other authors. 2003; Induction of neutralizing antibodies and partial protection from viral challenge in Macaca fascicularis immunized with recombinant dengue 4 virus envelope glycoprotein expressed in Pichia pastoris . Am J Trop Med Hyg 69:129–134[PubMed]
    [Google Scholar]
  26. Hanke T., Szawlowski P., Randall R.E. 1992; Construction of solid matrix-antibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen. J Gen Virol 73:653–660 [View Article][PubMed]
    [Google Scholar]
  27. Henchal E.A., McCown J.M., Burke D.S., Seguin M.C., Brandt W.E. 1985; Epitopic analysis of antigenic determinants on the surface of dengue-2 virions using monoclonal antibodies. Am J Trop Med Hyg 34:162–169
    [Google Scholar]
  28. Hon H., Oran A., Brocker T., Jacob J. 2005; B lymphocytes participate in cross-presentation of antigen following gene gun vaccination. J Immunol 174:5233–5242 [View Article][PubMed]
    [Google Scholar]
  29. Hsieh S.C., Tsai W.Y., Nerurkar V.R., Wang W.K. 2014; Characterization of the ectodomain of the envelope protein of dengue virus type 4: expression, membrane association, secretion and particle formation in the absence of precursor membrane protein. PLoS One 9:e100641 [View Article][PubMed]
    [Google Scholar]
  30. Khan K.H. 2013; DNA vaccines: roles against diseases. Germs 3:26–35 [View Article][PubMed]
    [Google Scholar]
  31. Khanam S., Khanna N., Swaminathan S. 2006; Induction of neutralizing antibodies and T cell responses by dengue virus type 2 envelope domain III encoded by plasmid and adenoviral vectors. Vaccine 24:6513–6525 [View Article][PubMed]
    [Google Scholar]
  32. Klein D.E., Choi J.L., Harrison S.C. 2013; Structure of a dengue virus envelope protein late-stage fusion intermediate. J Virol 87:2287–2293 [View Article][PubMed]
    [Google Scholar]
  33. Konishi E., Kosugi S., Imoto J. 2006; Dengue tetravalent DNA vaccine inducing neutralizing antibody and anamnestic responses to four serotypes in mice. Vaccine 24:2200–2207 [View Article][PubMed]
    [Google Scholar]
  34. Ledgerwood J.E., Pierson T.C., Hubka S.A., Desai N., Rucker S., Gordon I.J., Enama M.E., Nelson S., Nason M., other authors. 2011; A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial. J Infect Dis 203:1396–1404 [View Article][PubMed]
    [Google Scholar]
  35. Li E., Pedraza A., Bestagno M., Mancardi S., Sanchez R., Burrone O. 1997; Mammalian cell expression of dimeric small immune proteins (SIP). Protein Eng 10:731–736 [View Article][PubMed]
    [Google Scholar]
  36. Li L., Lok S.M., Yu I.M., Zhang Y., Kuhn R.J., Chen J., Rossmann M.G. 2008; The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science 319:1830–1834 [View Article][PubMed]
    [Google Scholar]
  37. Li X., Cao H., Wang Q., Di B., Wang M., Lu J., Pan L., Yang L., Mei M., other authors. 2012; Novel AAV-based genetic vaccines encoding truncated dengue virus envelope proteins elicit humoral immune responses in mice. Microbes Infect 14:1000–1007 [View Article][PubMed]
    [Google Scholar]
  38. Liao M., Sánchez-San Martín C., Zheng A., Kielian M. 2010; In vitro reconstitution reveals key intermediate states of trimer formation by the dengue virus membrane fusion protein. J Virol 84:5730–5740 [View Article][PubMed]
    [Google Scholar]
  39. Lima D.M., de Paula S.O., França R.F., Palma P.V., Morais F.R., Gomes-Ruiz A.C., de Aquino M.T., da Fonseca B.A. 2011; A DNA vaccine candidate encoding the structural prM/E proteins elicits a strong immune response and protects mice against dengue-4 virus infection. Vaccine 29:831–838 [View Article][PubMed]
    [Google Scholar]
  40. Lin H.E., Tsai W.Y., Liu I.J., Li P.C., Liao M.Y., Tsai J.J., Wu Y.C., Lai C.Y., Lu C.H., other authors. 2012; Analysis of epitopes on dengue virus envelope protein recognized by monoclonal antibodies and polyclonal human sera by a high throughput assay. PLoS Negl Trop Dis 6:e1447 [View Article][PubMed]
    [Google Scholar]
  41. Lindenbach B.D., Heinz-Jurgen T., Rice C.M. 2007; Flaviviridae: the viruses and their replication. In Fields’ Virology, 5th edn.. pp. 1126–1131 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott-Raven;
    [Google Scholar]
  42. Lok S.M., Kostyuchenko V., Nybakken G.E., Holdaway H.A., Battisti A.J., Sukupolvi-Petty S., Sedlak D., Fremont D.H., Chipman P.R., other authors. 2008; Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol 15:312–317 [View Article][PubMed]
    [Google Scholar]
  43. MacGregor R.R., Boyer J.D., Ugen K.E., Lacy K.E., Gluckman S.J., Bagarazzi M.L., Chattergoon M.A., Baine Y., Higgins T.J., other authors. 1998; First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. J Infect Dis 178:92–100 [View Article][PubMed]
    [Google Scholar]
  44. Mani S., Tripathi L., Raut R., Tyagi P., Arora U., Barman T., Sood R., Galav A., Wahala W., other authors. 2013; Pichia pastoris-expressed dengue 2 envelope forms virus-like particles without pre-membrane protein and induces high titer neutralizing antibodies. PLoS One 8:e64595 [View Article][PubMed]
    [Google Scholar]
  45. Martin J.E., Sullivan N.J., Enama M.E., Gordon I.J., Roederer M., Koup R.A., Bailer R.T., Chakrabarti B.K., Bailey M.A., other authors. 2006; A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol 13:1267–1277 [View Article][PubMed]
    [Google Scholar]
  46. Martin J.E., Pierson T.C., Hubka S., Rucker S., Gordon I.J., Enama M.E., Andrews C.A., Xu Q., Davis B.S., other authors. 2007; A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis 196:1732–1740 [View Article][PubMed]
    [Google Scholar]
  47. Matsui K., Gromowski G.D., Li L., Schuh A.J., Lee J.C., Barrett A.D. 2009; Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain III. Virology 384:16–20 [View Article][PubMed]
    [Google Scholar]
  48. Modis Y. 2014; Relating structure to evolution in class II viral membrane fusion proteins. Curr Opin Virol 5:34–41 [View Article][PubMed]
    [Google Scholar]
  49. Modis Y., Ogata S., Clements D., Harrison S.C. 2005; Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol 79:1223–1231 [View Article][PubMed]
    [Google Scholar]
  50. Monath T.P., Arroyo J., Levenbook I., Zhang Z.X., Catalan J., Draper K., Guirakhoo F. 2002; Single mutation in the flavivirus envelope protein hinge region increases neurovirulence for mice and monkeys but decreases viscerotropism for monkeys: relevance to development and safety testing of live, attenuated vaccines. J Virol 76:1932–1943 [View Article][PubMed]
    [Google Scholar]
  51. Mukhopadhyay S., Kuhn R.J., Rossmann M.G. 2005; A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3:13–22 [View Article][PubMed]
    [Google Scholar]
  52. Murray N.E., Quam M.B., Wilder-Smith A. 2013; Epidemiology of dengue: past, present and future prospects. Clin Epidemiol 5:299–309[PubMed]
    [Google Scholar]
  53. Naish S., Dale P., Mackenzie J.S., McBride J., Mengersen K., Tong S. 2014; Climate change and dengue: a critical and systematic review of quantitative modelling approaches. BMC Infect Dis 14:167 [View Article][PubMed]
    [Google Scholar]
  54. Ninth Report of the International Committee on Taxonomy of Viruses 2012; Family-Flaviviridae. In. Virus Taxonomy pp. 1003–1020 Edited by A. M. Q. King, M. J. Adams, E. B. Carstens & E. J San Diego: Elsevier Science;
    [Google Scholar]
  55. Ocazionez Jimenez R., Lopes da Fonseca B.A. 2000; Recombinant plasmid expressing a truncated dengue-2 virus E protein without co-expression of prM protein induces partial protection in mice. Vaccine 19:648–654 [View Article]
    [Google Scholar]
  56. Petris G., Bestagno M., Arnoldi F., Burrone O.R. 2014; New tags for recombinant protein detection and O-glycosylation reporters. PLoS One 9:e96700 [View Article][PubMed]
    [Google Scholar]
  57. Pierson T.C., Fremont D.H., Kuhn R.J., Diamond M.S. 2008; Structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development. Cell Host Microbe 4:229–238 [View Article][PubMed]
    [Google Scholar]
  58. Poggianella M., Slon Campos J.L., Chan K.R., Tan H.C., Bestagno M., Ooi E.E., Burrone O.R. 2015; Dengue E protein domain III-based DNA immunisation induces strong antibody responses to all four viral serotypes. PLoS Negl Trop Dis 9:e0003947 [View Article][PubMed]
    [Google Scholar]
  59. Predonzani A., Arnoldi F., López-Requena A., Burrone O.R. 2008; In vivo site-specific biotinylation of proteins within the secretory pathway using a single vector system. BMC Biotechnol 8:41 [View Article][PubMed]
    [Google Scholar]
  60. Prompetchara E., Ketloy C., Keelapang P., Sittisombut N., Ruxrungtham K. 2014; Induction of neutralizing antibody response against four dengue viruses in mice by intramuscular electroporation of tetravalent DNA vaccines. PLoS One 9:e92643 [View Article][PubMed]
    [Google Scholar]
  61. Ramanathan M.P., Kuo Y.C., Selling B.H., Li Q., Sardesai N.Y., Kim J.J., Weiner D.B. 2009; Development of a novel DNA SynCon tetravalent dengue vaccine that elicits immune responses against four serotypes. Vaccine 27:6444–6453 [View Article][PubMed]
    [Google Scholar]
  62. Raviprakash K., Kochel T.J., Ewing D., Simmons M., Phillips I., Hayes C.G., Porter K.R. 2000; Immunogenicity of dengue virus type 1 DNA vaccines expressing truncated and full length envelope protein. Vaccine 18:2426–2434 [View Article][PubMed]
    [Google Scholar]
  63. Raviprakash K., Marques E., Ewing D., Lu Y., Phillips I., Porter K.R., Kochel T.J., August T.J., Hayes C.G., Murphy G.S. 2001; Synergistic neutralizing antibody response to a dengue virus type 2 DNA vaccine by incorporation of lysosome-associated membrane protein sequences and use of plasmid expressing GM-CSF. Virology 290:74–82 [View Article][PubMed]
    [Google Scholar]
  64. Raviprakash K., Apt D., Brinkman A., Skinner C., Yang S., Dawes G., Ewing D., Wu S.J., Bass S., other authors. 2006; A chimeric tetravalent dengue DNA vaccine elicits neutralizing antibody to all four virus serotypes in rhesus macaques. Virology 353:166–173 [View Article][PubMed]
    [Google Scholar]
  65. Rey F.A., Heinz F.X., Mandl C., Kunz C., Harrison S.C. 1995; The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375:291–298 [View Article][PubMed]
    [Google Scholar]
  66. Rodenhuis-Zybert I.A., van der Schaar H.M., da Silva Voorham J.M., van der Ende-Metselaar H., Lei H.Y., Wilschut J., Smit J.M. 2010; Immature dengue virus: a veiled pathogen?. PLoS Pathog 6:e1000718 [View Article][PubMed]
    [Google Scholar]
  67. Rothman A.L. 2011; Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11:532–543 [View Article][PubMed]
    [Google Scholar]
  68. Rouvinski A., Guardado-Calvo P., Barba-Spaeth G., Duquerroy S., Vaney M.C., Kikuti C.M., Navarro Sanchez M.E., Dejnirattisai W., Wongwiwat W., other authors. 2015; Recognition determinants of broadly neutralizing human antibodies against dengue viruses. Nature 520:109–113 [View Article][PubMed]
    [Google Scholar]
  69. Saenz R., Messmer B., Futalan D., Tor Y., Larsson M., Daniels G., Esener S., Messmer D. 2014; Activity of the HMGB1-derived immunostimulatory peptide Hp91 resides in the helical C-terminal portion and is enhanced by dimerization. Mol Immunol 57:191–199 [View Article][PubMed]
    [Google Scholar]
  70. Sambrook J., Fritsch E.F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual New York: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  71. Sarwar U.N., Costner P., Enama M.E., Berkowitz N., Hu Z., Hendel C.S., Sitar S., Plummer S., Mulangu S., other authors. 2015; Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial. J Infect Dis 211:549–557 [View Article][PubMed]
    [Google Scholar]
  72. Schibli D.J., Weissenhorn W. 2004; Class I and class II viral fusion protein structures reveal similar principles in membrane fusion. Mol Membr Biol 21:361–371 [View Article][PubMed]
    [Google Scholar]
  73. Shedlock D.J., Weiner D.B. 2000; DNA vaccination: antigen presentation and the induction of immunity. J Leukoc Biol 68:793–806[PubMed]
    [Google Scholar]
  74. Simmons C.P., Farrar J.J., Nguyen V., Wills B. 2012; Dengue. N Engl J Med 366:1423–1432 [View Article][PubMed]
    [Google Scholar]
  75. Sukupolvi-Petty S., Austin S.K., Engle M., Brien J.D., Dowd K.A., Williams K.L., Johnson S., Rico-Hesse R., Harris E., other authors. 2010; Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2. J Virol 84:9227–9239 [View Article][PubMed]
    [Google Scholar]
  76. Tsai W.Y., Hsieh S.C., Lai C.Y., Lin H.E., Nerurkar V.R., Wang W.K. 2012; C-terminal helical domains of dengue virus type 4 E protein affect the expression/stability of prM protein and conformation of prM and E proteins. PLoS One 7:e52600 [View Article][PubMed]
    [Google Scholar]
  77. Vaughn D.W., Scherer J.M., Sun W. 2008; Resistance to infection. In Dengue pp. 123–169 Edited by Halstead S. B. London: Imperial College Press; [View Article]
    [Google Scholar]
  78. Wahala W.M., Silva A.M. 2011; The human antibody response to dengue virus infection. Viruses 3:2374–2395 [View Article][PubMed]
    [Google Scholar]
  79. Wahala W.M., Kraus A.A., Haymore L.B., Accavitti-Loper M.A., de Silva A.M. 2009; Dengue virus neutralization by human immune sera: role of envelope protein domain III-reactive antibody. Virology 392:103–113 [View Article][PubMed]
    [Google Scholar]
  80. Weaver S.C., Vasilakis N. 2009; Molecular evolution of dengue viruses: contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease. Infect Genet Evol 9:523–540 [View Article][PubMed]
    [Google Scholar]
  81. WHO 2009 Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control Geneva: World Health Organization Press;
    [Google Scholar]
  82. Williams K.L., Wahala W.M., Orozco S., de Silva A.M., Harris E. 2012; Antibodies targeting dengue virus envelope domain III are not required for serotype-specific protection or prevention of enhancement in vivo . Virology 429:12–20 [View Article][PubMed]
    [Google Scholar]
  83. Zhang W., Chipman P.R., Corver J., Johnson P.R., Zhang Y., Mukhopadhyay S., Baker T.S., Strauss J.H., Rossmann M.G., Kuhn R.J. 2003; Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol 10:907–912 [View Article][PubMed]
    [Google Scholar]
  84. Zhang Y., Zhang W., Ogata S., Clements D., Strauss J.H., Baker T.S., Kuhn R.J., Rossmann M.G. 2004; Conformational changes of the flavivirus E glycoprotein. Structure 12:1607–1618 [View Article][PubMed]
    [Google Scholar]
  85. Zheng A., Umashankar M., Kielian M. 2010; In vitro and in vivo studies identify important features of dengue virus pr-E protein interactions. PLoS Pathog 6:e1001157 [View Article][PubMed]
    [Google Scholar]
  86. Zompi S., Santich B.H., Beatty P.R., Harris E. 2012; Protection from secondary dengue virus infection in a mouse model reveals the role of serotype cross-reactive B and T cells. J Immunol 188:404–416 [View Article][PubMed]
    [Google Scholar]
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