Immunity to dengue virus: A tale of original antigenic sin and tropical cytokine storms

Nature Reviews Immunology

Volumn 11, Issue 8, 2011, Pages 532-543

  Rothman, Alan L ^a  

^a UNIVERSITY OF RHODE ISLAND   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DENGUE VACCINE; GLYCOPROTEIN E; M PROTEIN; NONSTRUCTURAL PROTEIN 1;

ANTIBODY RESPONSE; DENGUE; DENGUE VIRUS; DISEASE COURSE; DRUG DEVELOPMENT; DRUG MECHANISM; DRUG RESEARCH; HUMAN; IMMUNE RESPONSE; IMMUNITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SEROTYPE; T LYMPHOCYTE;

ANIMALS; ANTIGENS, VIRAL; CYTOKINES; DENGUE; DENGUE VACCINES; DENGUE VIRUS; HUMANS;

EID: 79960835805     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri3014     Document Type: Review

References (117)

1. World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. New edition 2009. WHO [online], http://whqlibdoc.who. int/publications/2009/9789241547871-eng.pdf (2009).
2. Jessie, K., Fong, M. Y., Devi, S., Lam, S. K. & Wong, K. T. Localization of dengue virus in naturally infected human tissues, by immunohistochemistry and in situ hybridization. J. Infect. Dis. 189, 1411-1418 (2004). (Pubitemid 38543590)
3. Durbin, A. P. et al. Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever. Virology 376, 429-435 (2008).
4. La Ruche, G. et al. First two autochthonous dengue virus infections in metropolitan France, September 2010. Euro Surveill. 15, 19676 (2010).
5. Centers for Disease Control and Prevention. Locally acquired dengue-Key West, Florida, 2009-2010. MMWR Morb. Mortal. Wkly Rep. 59, 577-581 (2010).
6. Srikiatkhachorn, A. & Green, S. Markers of dengue disease severity. Curr. Top. Microbiol. Immunol. 338, 67-82 (2010).
7. Sabin, A. B. Research on dengue during World War II. Am. J. Trop. Med. Hyg. 1, 30-50 (1952).
8. Burke, D. S., Nisalak, A., Johnson, D. E. & Scott, R. M. A prospective study of dengue infections in Bangkok. Am. J. Trop. Med. Hyg. 38, 172-180 (1988). (Pubitemid 18036130)
9. Thein, S. et al. Risk factors in dengue shock syndrome. Am. J. Trop. Med. Hyg. 56, 566-572 (1997). (Pubitemid 27230081)
10. Graham, R. R. et al. A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995-1996. Am. J. Trop. Med. Hyg. 61, 412-419 (1999). (Pubitemid 29428712)
11. Halstead, S. B., Scanlon, J. E., Umpaivit, P. & Udomsakdi, S. Dengue and chikungunya virus infection in man in Thailand, 1962-1964 IV. Epidemiologic studies in the Bangkok metropolitan area. Am. J. Trop. Med. Hyg. 18, 997-1021 (1969).
12. Libraty, D. H. et al. A prospective nested case-control study of dengue in infants: rethinking and refining the antibody-dependent enhancement dengue hemorrhagic fever model. PLoS Med. 6, e1000171 (2009).
13. Wang, E. et al. Evolutionary relationships of endemic/epidemic and sylvatic dengue viruses. J. Virol. 74, 3227-3234 (2000). (Pubitemid 30143747)
14. Yauch, L. E. & Shresta, S. Mouse models of dengue virus infection and disease. Antiviral Res. 80, 87-93 (2008).
15. Bente, D. A., Melkus, M. W., Garcia, J. V. & Rico-Hesse, R. Dengue fever in humanized NOD/SCID mice. J. Virol. 79, 13797-13799 (2005). (Pubitemid 41508191)
16. Jaiswal, S. et al. Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rγnull mice. PLoS ONE 4, e7251 (2009).
17. Valdes, K. et al. Human dengue antibodies against structural and nonstructural proteins. Clin. Diagn. Lab. Immunol. 7, 856-857 (2000).
18. Churdboonchart, V., Bhamarapravati, N., Peampramprecha, S. & Sirinavin, S. Antibodies against dengue viral proteins in primary and secondary dengue hemorrhagic fever. Am. J. Trop. Med. Hyg. 44, 481-493 (1991).
19. Roehrig, J. T., Bolin, R. A. & Kelly, R. G. Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 246, 317-328 (1998). (Pubitemid 28384045)
20. Sukupolvi-Petty, S. et al. Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2. J. Virol. 84, 9227-9239 (2010).
21. Kaufmann, B. et al. West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody. Proc. Natl Acad. Sci. USA 103, 12400-12404 (2006). (Pubitemid 44267271)
22. Lok, S. M. et al. Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nature Struct. Mol. Biol. 15, 312-317 (2008).
23. Cherrier, M. V. et al. Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody. EMBO J. 28, 3269-3276 (2009).
24. Lai, C. Y. et al. Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II. J. Virol. 82, 6631-6643 (2008).
25. Schieffelin, J. S. et al. Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient. Virol. J. 7, 28 (2010).
26. Beltramello, M. et al. The human immune response to dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity. Cell Host Microbe 8, 271-283 (2010).
27. Wahala, W. M., Kraus, A. A., Haymore, L. B., Accavitti-Loper, M. A. & de Silva, A. M. Dengue virus neutralization by human immune sera: role of envelope protein domain III-reactive antibody. Virology 392, 103-113 (2009).
28. Stadler, K., Allison, S. L., Schalich, J. & Heinz, F. X. Proteolytic activation of tick-borne encephalitis virus by furin. J. Virol. 71, 8475-8481 (1997). (Pubitemid 27446428)
29. Kuhn, R. J. et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108, 717-725 (2002). (Pubitemid 34241430)
30. Dejnirattisai, W. et al. Cross-reacting antibodies enhance dengue virus infection in humans. Science 328, 745-748 (2010).
31. Jacobs, M. G., Robinson, P. J., Bletchly, C., Mackenzie, J. M. & Young, P. R. Dengue virus nonstructural protein 1 is expressed in a glycosyl-phosphatidylinositol-linked form that is capable of signal transduction. FASEB J. 14, 1603-1610 (2000). (Pubitemid 30639071)
32. Young, P. R., Hilditch, P. A., Bletchly, C. & Halloran, W. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients. J. Clin. Microbiol. 38, 1053-1057 (2000). (Pubitemid 30140558)
33. Libraty, D. H. et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J. Infect. Dis. 186, 1165-1168 (2002). (Pubitemid 35177121)
34. Nybakken, G. E. et al. Structural basis of West Nile virus neutralization by a therapeutic antibody. Nature 437, 764-769 (2005). (Pubitemid 41486548)
35. Vogt, M. R. et al. Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step. J. Virol. 83, 6494-6507 (2009).
36. Pierson, T. C. et al. The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection. Cell Host Microbe 1, 135-145 (2007). (Pubitemid 46554914)
37. Thomas, S. J. et al. Dengue plaque reduction neutralization test (PRNT) in primary and secondary dengue virus infections: how alterations in assay conditions impact performance. Am. J. Trop. Med. Hyg. 81, 825-833 (2009).
38. Ubol, S., Phuklia, W., Kalayanarooj, S. & Modhiran, N. Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies. J. Infect. Dis. 201, 923-935 (2010).
39. Boonnak, K., Dambach, K. M., Donofrio, G. C., Tassaneetrithep, B. & Marovich, M. A. Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection. J. Virol. 85, 1671-1683 (2011).
40. Mehlhop, E. et al. Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner. Cell Host Microbe 2, 417-426 (2007). (Pubitemid 350215325)
41. Schlesinger, J. J., Brandriss, M. W. & Walsh, E. E. Protection of mice against dengue 2 virus encephalitis by immunization with the dengue 2 virus non-structural glycoprotein NS1. J. Gen. Virol. 68, 853-857 (1987). (Pubitemid 17021460)
42. Garcia, G. et al. Antibodies from patients with dengue viral infection mediate cellular cytotoxicity. J. Clin. Virol. 37, 53-57 (2006). (Pubitemid 44279527)
43. Laoprasopwattana, K. et al. Antibody dependent cellular cytotoxicity in pre-secondary dengue virus serotype 3 (DV3) but not in DV2 infection plasma samples inversely correlated with viremia levels. J. Infect. Dis. 195, 1108-1116 (2007).
44. Vaughan, K., Greenbaum, J., Blythe, M., Peters, B. & Sette, A. Meta-analysis of all immune epitope data in the Flavivirus genus: inventory of current immune epitope data status in the context of virus immunity and immunopathology. Viral Immunol. 23, 259-284 (2010).
45. Duangchinda, T. et al. Immunodominant T-cell responses to dengue virus NS3 are associated with DHF. Proc. Natl Acad. Sci. USA 107, 16922-16927 (2010).
46. Mangada, M. M. & Rothman, A. L. Altered cytokine responses of dengue-specific CD4+ T cells to heterologous serotypes. J. Immunol. 175, 2676-2683 (2005). (Pubitemid 41113883)
47. Bashyam, H. S., Green, S. & Rothman, A. L. Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes. J. Immunol. 176, 2817-2824 (2006).
48. Mongkolsapaya, J. et al. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nature Med. 9, 921-927 (2003). (Pubitemid 36889936)
49. Imrie, A. et al. Differential functional avidity of dengue virus-specific T-cell clones for variant peptides representing heterologous and previously encountered serotypes. J. Virol. 81, 10081-10091 (2007). (Pubitemid 350067712)
50. Rothman, A. L. & Ennis, F. A. in Dengue Tropical Medicine: Science and Practice (ed. Halstead, S. B.) 257-283 (Imperial College Press, London, 2008).
51. Kurane, I., Meager, A. & Ennis, F. A. Dengue virus-specific human T cell clones. Serotype crossreactive proliferation, interferon γ production, and cytotoxic activity. J. Exp. Med. 170, 763-775 (1989). (Pubitemid 19226663)
52. Bukowski, J. F. et al. Dengue virus-specific cross-reactive CD8+ human cytotoxic T lymphocytes. J. Virol. 63, 5086-5091 (1989). (Pubitemid 19278745)
53. Dong, T. et al. High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection. PLoS ONE 2, e1192 (2007).
54. Zivny, J. et al. Partial agonist effect influences the CTL response to a heterologous dengue virus serotype. J. Immunol. 163, 2754-2760 (1999). (Pubitemid 29399202)
55. Friberg, H. et al. Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive. Immunol. Cell Biol. 89, 122-129 (2011).
56. Matheus, S. et al. Discrimination between primary and secondary dengue virus infection by an immunoglobulin G avidity test using a single acute-phase serum sample. J. Clin. Microbiol. 43, 2793-2797 (2005). (Pubitemid 40827955)
57. Halstead, S. B., Rojanasuphot, S. & Sangkawibha, N. Original antigenic sin in dengue. Am. J. Trop. Med. Hyg. 32, 154-156 (1983). (Pubitemid 13186851)
58. van Panhuis, W. G. et al. Inferring the serotype associated with dengue virus infections on the basis of pre-and postinfection neutralizing antibody titers. J. Infect. Dis. 202, 1002-1010 (2010).
59. Midgley, C. M. et al. An in-depth analysis of original antigenic sin in dengue virus infection. J. Virol. 85, 410-421 (2011).
60. Kurane, I. et al. Human T cell responses to dengue virus antigens. Proliferative responses and interferon γ production. J. Clin. Invest. 83, 506-513 (1989). (Pubitemid 19061171)
61. Mathew, A. et al. Predominance of HLA-restricted CTL responses to serotype crossreactive epitopes on nonstructural proteins after natural dengue virus infections. J. Virol. 72, 3999-4004 (1998). (Pubitemid 28188703)
62. Kaufman, B. M. et al. Monoclonal antibodies for dengue virus prM glycoprotein protect mice against lethal dengue infection. Am. J. Trop. Med. Hyg. 41, 576-580 (1989). (Pubitemid 20000630)
63. Brien, J. D. et al. Genotype-specific neutralization and protection by antibodies against dengue virus type 3. J. Virol. 84, 10630-10643 (2010).
64. Lai, C. J. et al. Epitope determinants of a chimpanzee dengue virus type 4 (DENV-4)-neutralizing antibody and protection against DENV-4 challenge in mice and rhesus monkeys by passively transferred humanized antibody. J. Virol. 81, 12766-12774 (2007).
65. Henchal, E. A., Henchal, L. S. & Schlesinger, J. J. Synergistic interactions of anti-NS1 monoclonal antibodies protect passively immunized mice from lethal challenge with dengue 2 virus. J. Gen. Virol. 69, 2101-2107 (1988).
66. Kliks, S. C., Nisalak, A., Brandt, W. E., Wahl, L. & Burke, D. S. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am. J. Trop. Med. Hyg. 40, 444-451 (1989). (Pubitemid 19117544)
67. Endy, T. P. et al. Relationship of pre-existing dengue virus (DV) neutralizing antibody levels to viremia and disease severity in a prospective cohort study of DV infection in Thailand. J. Infect. Dis. 189, 990-1000 (2004). (Pubitemid 38373090)
68. An, J. et al. Dengue-specific CD8+ T cells have both protective and pathogenic roles in dengue virus infection. Immunol. Lett. 95, 167-174 (2004). (Pubitemid 39237662)
69. Yauch, L. E. et al. A protective role for dengue virus-specific CD8+ T cells. J. Immunol. 182, 4865-4873 (2009).
70. Gil, L. et al. Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice. Int. Immunol. 21, 1175-1183 (2009).
71. Lazo, L. et al. Nucleocapsid-like particles of dengue-2 virus enhance the immune response against a recombinant protein of dengue-4 virus. Arch. Virol. 155, 1587-1595 (2010).
72. Mangada, M. M. et al. Dengue-specific T cell responses in peripheral blood mononuclear cells obtained prior to secondary dengue virus infections in Thai schoolchildren. J. Infect. Dis. 185, 1697-1703 (2002). (Pubitemid 34615461)
73. Hatch, S. et al. Intracellular cytokine production by dengue virus-specific T cells correlates with subclinical secondary infection. J. Infect. Dis. 203, 1282-1291 (2011).
74. Gunther, V. J. et al. A human challenge model for dengue infection reveals a possible protective role for sustained interferon γ levels during the acute phase of illness. Vaccine 29, 3895-3904 (2011).
75. Stephens, H. A. HLA and other gene associations with dengue disease severity. Curr. Top. Microbiol. Immunol. 338, 99-114 (2010).
76. Goncalvez, A. P., Engle, R. E., St. Claire, M., Purcell, R. H. & Lai, C. J. Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc. Natl Acad. Sci. USA 104, 9422-9427 (2007). (Pubitemid 47185795)
77. Zellweger, R. M., Prestwood, T. R. & Shresta, S. Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe 7, 128-139 (2010).
78. Kliks, S. Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness. AIDS Res. Hum. Retroviruses 6, 993-998 (1990). (Pubitemid 20300059)
79. Kliks, S. C., Nimmanitya, S., Nisalak, A. & Burke, D. S. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am. J. Trop. Med. Hyg. 38, 411-419 (1988). (Pubitemid 18086128)
80. Laoprasopwattana, K. et al. Dengue virus (DV) enhancing antibody activity in preillness plasma does not predict subsequent disease severity or viremia in secondary DV infection. J. Infect. Dis. 192, 510-519 (2005). (Pubitemid 41023132)
81. Vaughn, D. W. et al. Dengue viremia titer, antibody response pattern and virus serotype correlate with disease severity. J. Infect. Dis. 181, 2-9 (2000). (Pubitemid 30049026)
82. Vaughn, D. W. et al. Dengue in the early febrile phase: viremia and antibody responses. J. Infect. Dis. 176, 322-330 (1997). (Pubitemid 27328753)
83. Libraty, D. H. et al. Differing influences of viral burden and immune activation on disease severity in secondary dengue 3 virus infections. J. Infect. Dis. 185, 1213-1221 (2002). (Pubitemid 34439127)
84. Malasit, P. Complement and dengue haemorrhagic fever/shock syndrome. Southeast Asian J. Trop. Med. Pub. Health 18, 316-320 (1987).
85. Avirutnan, P. et al. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. J. Infect. Dis. 193, 1078-1088 (2006).
86. Markoff, L. J., Innis, B. L., Houghten, R. & Henchal, L. S. Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection. J. Infect. Dis. 164, 294-301 (1991).
87. Falconar, A. K. I. The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesion proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis. Arch. Virol. 142, 897-916 (1997). (Pubitemid 27218413)
88. Dutcher, J. et al. Kidney cancer: the Cytokine Working Group experience (1986-2001): part II. Management of IL-2 toxicity and studies with other cytokines. Med. Oncol. 18, 209-219 (2001). (Pubitemid 33097348)
89. Yang, G. et al. The dual role of TNF in pulmonary edema. J. Cardiovasc. Dis. Res. 1, 29-36 (2010).
90. Kurane, I. et al. Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-γ in sera of children with dengue. J. Clin. Invest. 88, 1473-1480 (1991).
91. Green, S. et al. Early immune activation in acute dengue is related to development of plasma leakage and disease severity. J. Infect. Dis. 179, 755-762 (1999). (Pubitemid 29159319)
92. Green, S. et al. Early CD69 expression on peripheral blood lymphocytes from children with dengue hemorrhagic fever. J. Infect. Dis. 180, 1429-1435 (1999). (Pubitemid 29506442)
93. Chau, T. N. et al. Dengue in Vietnamese infants-results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity. J. Infect. Dis. 198, 516-524 (2008).
94. Green, S. et al. Elevated plasma interleukin-10 levels in acute dengue correlate with disease severity. J. Med. Virol. 59, 329-334 (1999). (Pubitemid 29468075)
95. Chiewsilp, P., Scott, R. M. & Bhamarapravati, N. Histocompatibility antigens and dengue hemorrhagic fever. Am. J. Trop. Med. Hyg. 30, 1100-1105 (1981).
96. Stephens, H. A. et al. HLA-A and-B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais. Tissue Antigens 60, 309-318 (2002). (Pubitemid 36020803)
97. Loke, H. et al. Strong HLA class I-restricted T cell responses in dengue hemorrhagic fever: a double-edged sword? J. Infect. Dis. 184, 1369-1373 (2001). (Pubitemid 33108849)
98. Sun, W. et al. Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naive adults. Hum. Vaccin. 5, 33-40 (2009).
99. Gwinn, W., Sun, W., Innis, B. L., Caudill, J. & King, A. D. Serotype-specific TH1 responses in recipients of two doses of candidate live-attenuated dengue virus vaccines. Am. J. Trop. Med. Hyg. 69, 39-47 (2003).
100. Kanesa-thasan, N. et al. Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers. Vaccine 19, 3179-3188 (2001).
101. Rothman, A. L. et al. Induction of T lymphocyte responses to dengue virus by a candidate tetravalent live attenuated dengue virus vaccine. Vaccine 19, 4694-4699 (2001). (Pubitemid 32800752)
102. Guirakhoo, F. et al. Viremia and immunogenicity in nonhuman primates of a tetravalent yellow fever-dengue chimeric vaccine: genetic reconstructions, dose adjustment, and antibody responses against wild-type dengue virus isolates. Virology 298, 146-159 (2002). (Pubitemid 34734888)
103. Morrison, D. et al. A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. J. Infect. Dis. 201, 370-377 (2010).
104. Guy, B. et al. Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects. Vaccine 26, 5712-5721 (2008).
105. Blaney, J. E. Jr, Durbin, A. P., Murphy, B. R. & Whitehead, S. S. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 19, 10-32 (2006).
106. Huang, C. Y. et al. Dengue 2 PDK-53 virus as a chimeric carrier for tetravalent dengue vaccine development. J. Virol. 77, 11436-11447 (2003). (Pubitemid 37271642)
107. Smucny, J. J., Kelly, E. P., Macarthy, P. O. & King, A. D. Murine immunoglobulin G subclass responses following immunization with live dengue virus or a recombinant dengue envelope protein. Am. J. Trop. Med. Hyg. 53, 432-437 (1995).
108. Beaumier, C. M. et al. Differential in vivo clearance and response to secondary heterologous infections by H2b-restricted dengue virus-specific CD8+ T cells. Viral Immunol. 23, 477-485 (2010).
109. Shresta, S. et al. Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T-and B-cell-dependent immunity are less critical. J. Virol. 78, 2701-2710 (2004). (Pubitemid 38314329)
110. Kaufman, B. M., Summers, P. L., Dubois, D. R. & Eckels, K. H. Monoclonal antibodies against dengue 2 virus E-glycoprotein protect mice against lethal dengue infection. Am. J. Trop. Med. Hyg. 36, 427-434 (1987). (Pubitemid 17057550)
111. Chen, H. C., Hofman, F. M., Kung, J. T., Lin, Y. D. & Wu-Hsieh, B. A. Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J. Virol. 81, 5518-5526 (2007). (Pubitemid 46846992)
112. Souza, D. G. et al. Essential role of platelet-activating factor receptor in the pathogenesis of dengue virus infection. Proc. Natl Acad. Sci. USA 106, 14138-14143 (2009).
113. Huang, K. J. et al. Manifestation of thrombocytopenia in dengue-2-virus-infected mice. J. Gen. Virol. 81, 2177-2182 (2000).
114. Johnson, A. J. & Roehrig, J. T. New mouse model for dengue virus vaccine testing. J. Virol. 73, 783-786 (1999). (Pubitemid 28565427)
115. Shresta, S., Sharar, K. L., Prigozhin, D. M., Beatty, P. R. & Harris, E. Murine model for dengue virus-induced lethal disease with increased vascular permeability. J. Virol. 80, 10208-10217 (2006). (Pubitemid 44522614)
116. Koraka, P., Benton, S., van Amerongen, G., Stittelaar, K. J. & Osterhaus, A. D. Efficacy of a live attenuated tetravalent candidate dengue vaccine in naive and previously infected cynomolgus macaques. Vaccine 25, 5409-5416 (2007). (Pubitemid 46977528)
117. Guirakhoo, F. et al. Safety and efficacy of chimeric yellow fever-dengue virus tetravalent vaccine formulations in nonhuman primates. J. Virol. 78, 4761-4775 (2004). (Pubitemid 38501097)