Skip to main content Accessibility help

Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection

  • Theodore C. Pierson (a1) and Michael S. Diamond (a2)


Flaviviruses are a group of positive-stranded RNA viruses that cause a spectrum of severe illnesses globally in more than 50 million individuals each year. While effective vaccines exist for three members of this group (yellow fever, Japanese encephalitis, and tick-borne encephalitis viruses), safe and effective vaccines for several other flaviviruses of clinical importance, including West Nile and dengue viruses, remain in development. An effective humoral immune response is critical for protection against flaviviruses and an essential goal of vaccine development. The effectiveness of virus-specific antibodies in vivo reflects their capacity to inhibit virus entry and spread through several mechanisms, including the direct neutralisation of virus infection. Recent advances in our understanding of the structural biology of flaviviruses, coupled with the use of small-animal models of flavivirus infection, have promoted significant advances in our appreciation of the factors that govern antibody recognition and inhibition of flaviviruses in vitro and in vivo. In this review, we discuss the properties that define the potency of neutralising antibodies and the molecular mechanisms by which they inhibit virus infection. How recent advances in this area have the potential to improve the development of safe and effective vaccines and immunotherapeutics is also addressed.


Corresponding author

*Corresponding author: Theodore C. Pierson, Laboratory of Viral Diseases, NIAID, NIH, 33 North Drive, Room 1E19A.2, Bethesda, MD 20814, USA. Tel: +1 301 451 7977; Fax: 1 301 451 7978; E-mail:


Hide All
1Mackenzie, J.S., Gubler, D.J. and Petersen, L.R. (2004) Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10, S98-109
2Zhang, Y. et al. (2004) Conformational changes of the flavivirus E glycoprotein. Structure 12, 1607-1618
3Rey, F.A. et al. (1995) The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375, 291-298
4Modis, Y. et al. (2003) A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A 100, 6986-6991
5Modis, Y. et al. (2005) Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol 79, 1223-1231
6Chu, J.J. et al. (2005) Inhibition of West Nile virus entry by using a recombinant domain III from the envelope glycoprotein. J Gen Virol 86, 405-412
7Allison, S.L. et al. (2001) Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J Virol 75, 4268-4275
8Modis, Y. et al. (2004) Structure of the dengue virus envelope protein after membrane fusion. Nature 427, 313-319
9Bressanelli, S. et al. (2004) Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J 23, 728-738
10Zhang, W. et al. (2003) Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol 10, 907-912
11Allison, S.L. et al. (1999) Mapping of functional elements in the stem-anchor region of tick-borne encephalitis virus envelope protein E. J Virol 73, 5605-5612
12Wang, S., He, R. and Anderson, R. (1999) PrM- and cell-binding domains of the dengue virus E protein. J Virol 73, 2547-2551
13Mackenzie, J.M. and Westaway, E.G. (2001) Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75, 10787-10799
14Zhang, Y. et al. (2007) Structure of immature West Nile virus. J Virol 81, 6141-6145
15Zhang, Y. et al. (2003) Structures of immature flavivirus particles. EMBO J 22, 2604-2613
16Heinz, F.X. et al. (1994) Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM. Virology 198, 109-117
17Guirakhoo, F. et al. (1991) Fusion activity of flaviviruses: comparison of mature and immature (prM-containing) tick-borne encephalitis virions. J Gen Virol 72, 1323-1329
18Mukhopadhyay, S., Kuhn, R.J. and Rossmann, M.G. (2005) A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3, 13-22
19Stadler, K. et al. (1997) Proteolytic activation of tick-borne encephalitis virus by furin. J Virol 71, 8475-8481
20Mukhopadhyay, S. et al. (2003) Structure of West Nile virus. Science 302, 248
21Kuhn, R.J. et al. (2002) Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108, 717-725
22Kimura, T., Gollins, S.W. and Porterfield, J.S. (1986) The effect of pH on the early interaction of West Nile virus with P388D1 cells. J Gen Virol 67, 2423-2433
23Gollins, S.W. and Porterfield, J.S. (1986) pH-dependent fusion between the flavivirus West Nile and liposomal model membranes. J Gen Virol 67, 157-166
24Holzmann, H. et al. (1995) Tick-borne encephalitis virus envelope protein E-specific monoclonal antibodies for the study of low pH-induced conformational changes and immature virions. Arch Virol 140, 213-221
25Stiasny, K. et al. (1996) Structural requirements for low-pH-induced rearrangements in the envelope glycoprotein of tick-borne encephalitis virus. J Virol 70, 8142-8147
26Stiasny, K. et al. (2001) Role of metastability and acidic pH in membrane fusion by tick-borne encephalitis virus. J Virol 75, 7392-7398
27Allison, S.L. et al. (1995) Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol 69, 695-700
28Eckert, D.M. and Kim, P.S. (2001) Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 70, 777-810
29Colman, P.M. and Lawrence, M.C. (2003) The structural biology of type I viral membrane fusion. Nat Rev Mol Cell Biol 4, 309-319
30Liao, M. and Kielian, M. (2005) Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion. J Cell Biol 171, 111-120
31Bai, F. et al. (2007) Antiviral peptides targeting the west nile virus envelope protein. J Virol 81, 2047-2055
32Hrobowski, Y.M., Garry, R.F. and Michael, S.F. (2005) Peptide inhibitors of dengue virus and West Nile virus infectivity. Virol J 2, 49
33Reeves, J.D. and Piefer, A.J. (2005) Emerging drug targets for antiretroviral therapy. Drugs 65, 1747-1766
34Diamond, M.S. et al. (2003) B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus. J Virol 77, 2578-2586
35Diamond, M.S. et al. (2003) Innate and adaptive immune responses determine protection against disseminated infection by West Nile encephalitis virus. Viral Immunol 16, 259-278
36Oliphant, T. et al. (2005) Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. Nat Med 11, 522-530
37Tesh, R.B. et al. (2002) Immunization with heterologous flaviviruses protective against fatal West Nile encephalitis. Emerg Infect Dis 8, 245-251
38Wang, T. et al. (2001) Immunization of mice against West Nile virus with recombinant envelope protein. J Immunol 167, 5273-5277
39Ben-Nathan, D. et al. (2003) Prophylactic and therapeutic efficacy of human intravenous immunoglobulin in treating west nile virus infection in mice. J Infect Dis 188, 5-12
40Camenga, D.L., Nathanson, N. and Cole, G.A. (1974) Cyclophosphamide-potentiated West Nile viral encephalitis: relative influence of cellular and humoral factors. J Infect Dis 130, 634-641
41Roehrig, J.T. et al. (2001) Antibody prophylaxis and therapy for flavivirus encephalitis infections. Ann N Y Acad Sci 951, 286-297
42Mathews, J.H. and Roehrig, J.T. (1984) Elucidation of the topography and determination of the protective epitopes on the E glycoprotein of Saint Louis encephalitis virus by passive transfer with monoclonal antibodies. J Immunol 132, 1533-1537
43Kreil, T.R. et al. (1997) Antibodies protect mice against challenge with tick-borne encephalitis virus (TBEV)-infected macrophages. Clin Exp Immunol 110, 358-361
44Kreil, T.R. et al. (1998) Neutralizing antibodies protect against lethal flavivirus challenge but allow for the development of active humoral immunity to a nonstructural virus protein. J Virol 72, 3076-3081
45Beasley, D.W. et al. (2004) Protection against Japanese encephalitis virus strains representing four genotypes by passive transfer of sera raised against ChimeriVax-JE experimental vaccine. Vaccine 22, 3722-3726
46Vazquez, S. et al. (2002) Immune response to synthetic peptides of dengue prM protein. Vaccine 20, 1823-1830
47Pincus, S. et al. (1992) Recombinant vaccinia virus producing the prM and E proteins of yellow fever virus protects mice from lethal yellow fever encephalitis. Virology 187, 290-297
48Falconar, A.K. (1999) Identification of an epitope on the dengue virus membrane (M) protein defined by cross-protective monoclonal antibodies: design of an improved epitope sequence based on common determinants present in both envelope (E and M) proteins. Arch Virol 144, 2313-2330
49Colombage, G. et al. (1998) DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus. Virology 250, 151-163
50Chung, K.M. et al. (2007) Antibody recognition of cell surface-associated NS1 triggers Fc-gamma receptor-mediated phagocytosis and clearance of West Nile Virus-infected cells. J Virol 81, 9551-9555
51Chung, K.M. et al. (2006) Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms. J Virol 80, 1340-1351
52Shu, P.Y. et al. (2000) Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with Dengue fever and Dengue hemorrhagic fever. J Med Virol 62, 224-232
53Churdboonchart, V. et al. (1991) Antibodies against dengue viral proteins in primary and secondary dengue hemorrhagic fever. Am J Trop Med Hyg 44, 481-493
54Gibson, C.A., Schlesinger, J.J. and Barrett, A.D. (1988) Prospects for a virus non-structural protein as a subunit vaccine. Vaccine 6, 7-9
55Beasley, D.W. and Barrett, A.D. (2002) Identification of neutralizing epitopes within structural domain III of the West Nile virus envelope protein. J Virol 76, 13097-13100
56Oliphant, T. et al. (2006) Antibody recognition and neutralization determinants on domains I and II of West Nile Virus envelope protein. J Virol 80, 12149-12159
57Crill, W.D. and Chang, G.J. (2004) Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes. J Virol 78, 13975-13986
58Roehrig, J.T., Bolin, R.A. and Kelly, R.G. (1998) Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 246, 317-328
59Roehrig, J.T., Mathews, J.H. and Trent, D.W. (1983) Identification of epitopes on the E glycoprotein of Saint Louis encephalitis virus using monoclonal antibodies. Virology 128, 118-126
60Heinz, F.X. et al. (1983) A topological and functional model of epitopes on the structural glycoprotein of tick-borne encephalitis virus defined by monoclonal antibodies. Virology 126, 525-537
61Mandl, C.W. et al. (1989) Antigenic structure of the flavivirus envelope protein E at the molecular level, using tick-borne encephalitis virus as a model. J Virol 63, 564-571
62Sukupolvi-Petty, S. et al. (2007) Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. J Virol 81, 12816-12826
63Throsby, M. et al. (2006) Isolation and characterization of human monoclonal antibodies from individuals infected with West Nile Virus. J Virol 80, 6982-6992
64Oliphant, T. et al. (2007) Induction of epitope-specific neutralizing antibodies against West Nile virus. J Virol 81, 11828-11839
65Sanchez, M.D. et al. (2007) The neutralizing antibody response against West Nile virus in naturally infected horses. Virology 359, 336-348
66Della-Porta, A.J. and Westaway, E.G. (1978) A multi-hit model for the neutralization of animal viruses. J Gen Virol 38, 1-19
67Burton, D.R., Saphire, E.O. and Parren, P.W. (2001) A model for neutralization of viruses based on antibody coating of the virion surface. Curr Top Microbiol Immunol 260, 109-143
68Pierson, T.C. et al. (2007) Stoichiometric requirements for antibody-mediated neutralization and enhancement of West Nile virus infection. Cell Host Microbe 1, 135-146
69Klasse, P.J. and Sattentau, Q.J. (2002) Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J Gen Virol 83, 2091-2108
70Gromowski, G.D. and Barrett, A.D. (2007) Characterization of an antigenic site that contains a dominant, type-specific neutralization determinant on the envelope protein domain III (ED3) of dengue 2 virus. Virology 366, 349-360
71Stiasny, K. et al. (2006) Cryptic properties of a cluster of dominant flavivirus cross-reactive antigenic sites. J Virol 80, 9557-9568
72Morrey, J.D. et al. (2006) Humanized monoclonal antibody against West Nile virus envelope protein administered after neuronal infection protects against lethal encephalitis in hamsters. J Infect Dis 194, 1300-1308
73Morrey, J.D. et al. (2007) Defining limits of treatment with humanized neutralizing monoclonal antibody for West Nile virus neurological infection in a hamster model. Antimicrob Agents Chemother 51, 2396-2402
74Nybakken, G.E. et al. (2005) Structural basis of West Nile virus neutralization by a therapeutic antibody. Nature 437, 764-769
75Kaufmann, B. et al. (2006) West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody. Proc Natl Acad Sci U S A 103, 12400-12404
76Krishnan, M.N. et al. (2007) Rab 5 is required for the cellular entry of dengue and West Nile viruses. J Virol 81, 4881-4885
77van der Schaar, H.M. et al. (2007) Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. J Virol 81, 12019-12028
78Gollins, S.W. and Porterfield, J.S. (1985) Flavivirus infection enhancement in macrophages: an electron microscopic study of viral cellular entry. J Gen Virol 66, 1969-1982
79Chu, J.J. and Ng, M.L. (2004) Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol 78, 10543-10555
80Anderson, R. (2003) Manipulation of cell surface macromolecules by flaviviruses. Adv Virus Res 59, 229-274
81Stiasny, K., Koessl, C. and Heinz, F.X. (2003) Involvement of lipids in different steps of the flavivirus fusion mechanism. J Virol 77, 7856-7862
82Stiasny, K. et al. (2002) Membrane interactions of the tick-borne encephalitis virus fusion protein E at low pH. J Virol 76, 3784-3790
83Pantophlet, R. and Burton, D.R. (2006) GP120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol 24, 739-769
84He, R.T. et al. (1995) Antibodies that block virus attachment to Vero cells are a major component of the human neutralizing antibody response against dengue virus type 2. J Med Virol 45, 451-461
85Jennings, A.D. et al. (1994) Analysis of a yellow fever virus isolated from a fatal case of vaccine-associated human encephalitis. J Infect Dis 169, 512-518
86Mandl, C.W. et al. (2000) Attenuation of tick-borne encephalitis virus by structure-based site-specific mutagenesis of a putative flavivirus receptor binding site. J Virol 74, 9601-9609
87Holzmann, H. et al. (1990) A single amino acid substitution in envelope protein E of tick-borne encephalitis virus leads to attenuation in the mouse model. J Virol 64, 5156-5159
88Jiang, W.R. et al. (1993) Single amino acid codon changes detected in louping ill virus antibody-resistant mutants with reduced neurovirulence. J Gen Virol 74, 931-935
89Tassaneetrithep, B. et al. (2003) DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med 197, 823-829
90Navarro-Sanchez, E. et al. (2003) Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep 4, 723-728
91Sakuntabhai, A. et al. (2005) A variant in the CD209 promoter is associated with severity of dengue disease. Nat Genet 37, 507-513
92Lozach, P.Y. et al. (2005) Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN)-mediated enhancement of dengue virus infection is independent of DC-SIGN internalization signals. J Biol Chem 280, 23698-23708
93Davis, C.W. et al. (2006) The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin). J Biol Chem 281, 37183-37194
94Davis, C.W. et al. (2006) West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection. J Virol 80, 1290-1301
95Pokidysheva, E. et al. (2006) Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Cell 124, 485-493
96Mitchell, D.A., Fadden, A.J. and Drickamer, K. (2001) A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem 276, 28939-28945
97Gollins, S.W. and Porterfield, J.S. (1986) A new mechanism for the neutralization of enveloped viruses by antiviral antibody. Nature 321, 244-246
98Nybakken, G.E. et al. (2006) Crystal structure of the west nile virus envelope glycoprotein. J Virol 80, 11467-11474
99Stiasny, K. et al. (2007) Probing the flavivirus membrane fusion mechanism by using monoclonal antibodies. J Virol 81, 11526-11531
100Mehlhop, E. et al. (2005) Complement activation is required for induction of a protective antibody response against West Nile virus infection. J Virol 79, 7466-7477
101Mehlhop, E. and Diamond, M.S. (2006) Protective immune responses against West Nile virus are primed by distinct complement activation pathways. J Exp Med 203, 1371-1381
102Meyer, K. et al. (2002) Complement-mediated enhancement of antibody function for neutralization of pseudotype virus containing hepatitis C virus E2 chimeric glycoprotein. J Virol 76, 2150-2158
103Feng, J.Q., Mozdzanowska, K. and Gerhard, W. (2002) Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype. J Virol 76, 1369-1378
104Schlesinger, J.J. and Chapman, S. (1995) Neutralizing F(ab')2 fragments of protective monoclonal antibodies to yellow fever virus (YF) envelope protein fail to protect mice against lethal YF encephalitis. J Gen Virol 76, 217-220
105Schlesinger, J.J., Foltzer, M. and Chapman, S. (1993) The Fc portion of antibody to yellow fever virus NS1 is a determinant of protection against YF encephalitis in mice. Virology 192, 132-141
106Halstead, S.B. (2003) Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60, 421-467
107Rothman, A.L. (2003) Immunology and immunopathogenesis of dengue disease. Adv Virus Res 60, 397-419
108Vaughn, D.W. et al. (2000) Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181, 2-9
109Halstead, S.B., Nimmannitya, S. and Cohen, S.N. (1970) Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med 42, 311-328
110Kliks, S.C. et al. (1988) Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38, 411-419
111Klimstra, W.B. et al. (2005) Targeting Sindbis virus-based vectors to Fc receptor-positive cell types. Virology 338, 9-21
112Iankov, I.D. et al. (2006) Immunoglobulin g antibody-mediated enhancement of measles virus infection can bypass the protective antiviral immune response. J Virol 80, 8530-8540
113Huang, K.J. et al. (2006) The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection. J Immunol 176, 2825-2832
114Wallace, M.J. et al. (2003) Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice. J Gen Virol 84, 1723-1728
115Takada, A. et al. (2003) Antibody-dependent enhancement of Ebola virus infection. J Virol 77, 7539-7544
116Girn, J., Kavoosi, M. and Chantler, J. (2002) Enhancement of coxsackievirus B3 infection by antibody to a different coxsackievirus strain. J Gen Virol 83, 351-358
117Littaua, R., Kurane, I. and Ennis, F.A. (1990) Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. J Immunol 144, 3183-3186
118Takeda, A., Tuazon, C.U. and Ennis, F.A. (1988) Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science 242, 580-583
119Tamura, M., Webster, R.G. and Ennis, F.A. (1991) Antibodies to HA and NA augment uptake of influenza A viruses into cells via Fc receptor entry. Virology 182, 211-219
120Morens, D.M. and Halstead, S.B. (1990) Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. J Gen Virol 71, 2909-2914
121Morens, D.M., Halstead, S.B. and Marchette, N.J. (1987) Profiles of antibody-dependent enhancement of dengue virus type 2 infection. Microb Pathog 3, 231-237
122Gimenez, H.B. et al. (1996) Neutralizing and enhancing activities of human respiratory syncytial virus-specific antibodies. Clin Diagn Lab Immunol 3, 280-286
123Gimenez, H.B., Keir, H.M. and Cash, P. (1989) In vitro enhancement of respiratory syncytial virus infection of U937 cells by human sera. J Gen Virol 70, 89-96
124Osiowy, C., Horne, D. and Anderson, R. (1994) Antibody-dependent enhancement of respiratory syncytial virus infection by sera from young infants. Clin Diagn Lab Immunol 1, 670-677
125Mady, B.J. et al. (1991) Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors. J Immunol 147, 3139-3144
126Gould, E.A. and Buckley, A. (1989) Antibody-dependent enhancement of yellow fever and Japanese encephalitis virus neurovirulence. J Gen Virol 70, 1605-1608
127Barrett, A.D. and Gould, E.A. (1986) Antibody-mediated early death in vivo after infection with yellow fever virus. J Gen Virol 67, 2539-2542
128Schlesinger, J.J. and Brandriss, M.W. (1981) Antibody-mediated infection of macrophages and macrophage-like cell lines with 17D-yellow fever virus. J Med Virol 8, 103-117
129Robinson, W.E. Jr., Montefiori, D.C. and Mitchell, W.M. (1988) Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet 1, 790-794
130Halstead, S.B. and O'Rourke, E.J. (1977) Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146, 201-217
131Goncalvez, A.P. et al. (2007) Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc Natl Acad Sci U S A 104, 9422-9427
132Halstead, S.B. (1979) In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. J Infect Dis 140, 527-533
133Mehlhop, E. et al. (2007) Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner. Cell Host Microbe 2, 417-426
134Broom, A.K. et al. (2000) Immunisation with gamma globulin to murray valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against australian encephalitis: evaluation in a mouse model. J Med Virol 61, 259-265
135Gollins, S.W. and Porterfield, J.S. (1984) Flavivirus infection enhancement in macrophages: radioactive and biological studies on the effect of antibody on viral fate. J Gen Virol 65, 1261-1272
136Chareonsirisuthigul, T., Kalayanarooj, S. and Ubol, S. (2007) Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells. J Gen Virol 88, 365-375
137Suhrbier, A. and La Linn, M. (2003) Suppression of antiviral responses by antibody-dependent enhancement of macrophage infection. Trends Immunol 24, 165-168
138Hober, D. et al. (2001) Antibody-dependent enhancement of coxsackievirus B4 infectivity of human peripheral blood mononuclear cells results in increased interferon-alpha synthesis. J Infect Dis 184, 1098-1108
139Lidbury, B.A. and Mahalingam, S. (2000) Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection. J Virol 74, 8376-8381
140Mahalingam, S. and Lidbury, B.A. (2003) Antibody-dependent enhancement of infection: bacteria do it too. Trends Immunol 24, 465-467
141Hamdan, A. et al. (2002) Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile virus encephalitis. Transpl Infect Dis 4, 160-162
142Shimoni, Z. et al. (2001) Treatment of West Nile virus encephalitis with intravenous immunoglobulin. Emerg Infect Dis 7, 759

Excellent general reviews on flaviviruses:

Whitehead, S.S. et al. (2007) Prospects for a dengue virus vaccine. Nat Rev Microbiol 5, 518-528
Mukhopadhyay, S., Kuhn, R.J. and Rossmann, M.G. (2005) A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3, 13-22
Stiasny, K. and Heinz, F.X. (2006) Flavivirus membrane fusion. J Gen Virol 87, 2755-2766
Mackenzie, J.S., Gubler, D.J. and Petersen, L.R. (2004) Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10, S98-109
Burton, D.R., Saphire, E.O. and Parren, P.W. (2001) A model for neutralization of viruses based on antibody coating of the virion surface. Curr Top Microbiol Immunol 260, 109-143
Della-Porta, A.J. and Westaway, E.G. (1978) A multi-hit model for the neutralization of animal viruses. J Gen Virol 38, 1-19
Klasse, P.J. and Sattentau, Q.J. (2002) Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J Gen Virol 83, 2091-2108
Smith, T.J. (2003) Structural studies on antibody-virus complexes. Adv Protein Chem 64, 409-453
Dimmock, N.J. (1993) Neutralization of animal viruses. Curr Top Microbiol Immunol 183, 1-149
Hangartner, L., Zinkernagel, R.M. and Hengartner, H. (2006) Antiviral antibody responses: the two extremes of a wide spectrum. Nat Rev Immunol 6, 231-243


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed