Profiles of antibody-dependent enhancement of dengue virus type 2 infection

Morens, David M.; Halstead, Scott B.; Marchette, Nyven J.

doi:10.1016/0882-4010(87)90056-8

Cited by 61 publications

(53 citation statements)

References 9 publications

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“…It is possible that the relatively high titre of homologous (TBE) antiserum (5-fold below the PRNT 50 titre for TBE) used by Kreil & Eibl (1997) in comparison to our study (heterologous JE antiserum diluted 10-fold and 100-fold below the PRNT 50 titre for MVE) may have been responsible for the different outcomes observed in these two studies. This is consistent with the observations of Morens et al (1987), who showed that inhibition of virus infection occurs when the ratio of neutralizing antibody to virus is high, whereas enhancement occurs when this ratio is reversed.…”

Section: Discussionsupporting

confidence: 81%

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice

Wallace

Smith²,

Broom

et al. 2003

Journal of General Virology

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Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.

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Section: Discussionsupporting

confidence: 81%

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice

Wallace

Smith²,

Broom

et al. 2003

Journal of General Virology

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“…However, if the neutralizing MAbs CR4348 and CR4354 recognized a structural protein on the virion, they should enhance infection in Fc-␥ receptor-expressing cells when the stoichiometry of binding falls below the neutralization threshold (51,66). The addition of subneutralizing concentrations of CR4348 and CR4354 to K562 cells that display human CD32 (Fc-␥RIIA) enhanced infection in a manner that was analogous to that observed with Hu-E16 (Fig.…”

Section: Characterization Of Strongly Neutralizing Human Mabsmentioning

confidence: 83%

Human Monoclonal Antibodies against West Nile Virus Induced by Natural Infection Neutralize at a Postattachment Step

Vogt¹,

Moesker

Goudsmit

et al. 2009

J Virol

105

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West Nile virus (WNV) is a neurotropic flavivirus that is now a primary cause of epidemic encephalitis inWNV cycles in nature between several species of birds and Culex mosquitoes, with humans and other mammals as deadend hosts (25, 62). Infection causes syndromes ranging from a mild febrile illness to severe encephalitis and death (13, 72). WNV has spread globally and causes outbreaks with thousands of severe human cases annually in the United States. An age of greater than 55 years, a compromised immune status, and a CC5⌬32 genotype have been associated with more-severe disease (15,20). There is currently no approved vaccine or therapy for WNV infection.The mature WNV virion has a ϳ500-Å diameter and consists of a single RNA genome surrounded by the capsid protein, a lipid bilayer, and a shell of the prM/M and E proteins (31, 55). X-ray crystallography studies have elucidated the three-domain structure of the flavivirus E protein (30,48,50,58,67). Domain I (DI) is a central, eight-stranded ␤-barrel, which contains the only N-linked glycosylation site in WNV E. Domain II (DII) is a long, finger-like protrusion from DI and contains the highly conserved fusion peptide at its distal end. Domain III (DIII) adopts an immunoglobulin-like fold at the opposite end of DI and is believed to contain a site for receptor attachment (6,8,40).Within an infected cell, progeny WNV are assembled initially as immature particles. In immature virions, three pairs of E and prM interact as trimers and form 60 spiked projections with icosahedral symmetry (85,86). Exposure to mildly acidic conditions in the trans-Golgi secretory pathway promotes virus maturation through a structural rearrangement of the E proteins and cleavage of prM to M by a furin-like protease (41,83). Mature WNV virions are covered by 90 antiparallel E protein homodimers, which are arranged flat along the surface in a herringbone pattern with quasi-icosahedral symmetry (55).Upon binding to poorly characterized cell surface receptors, internalization of WNV is believed to occur through receptormediated, clathrin-dependent endocytosis (1,79,80). After trafficking to 79), the mildly acidic pH within the lumen of the endosome induces structural alterations in the flavivirus E protein (7, 49), which includes changes in its oligomeric state (7,49,77). During this process, also known as type II fusion, the hydrophobic peptide on the fusion loop of DII of the E protein inserts into the

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“…Dengue virus is able to use these molecules as surrogate receptors. By the same mechanism, some high-affinity antibodies that neutralize virus of a certain serotype at high titers can increase cell uptake of the same serotype at sufficiently low antibody concentrations (3,16,38). The resulting enhancement of viral infection may cause more acute pathologies such as hemorrhagic fever (15,37).…”

Section: Implications For Immune Recognition Of Different Dengue Virumentioning

confidence: 99%

“…Lower-affinity antibodies will fail to neutralize, but they may still be present on virus particles in sufficient numbers to facilitate infection of cells bearing immunoglobulin G (IgG) Fc receptors (15,31). Alternatively, some high-affinity antibodies that are neutralizing at high titers can enhance infection at subneutralizing concentrations by facilitating cell uptake of virus of the cognate serotype (3,16,38).…”

mentioning

confidence: 99%

Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein

Modis

Ogata

Clements

et al. 2005

J Virol

387

360

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Dengue virus is an emerging global health threat. The major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. Antibodies that bind but fail to neutralize noncognate serotypes enhance infection. We have determined the crystal structure of a soluble fragment of the envelope glycoprotein E from dengue virus type 3. The structure closely resembles those of E proteins from dengue type 2 and tick-borne encephalitis viruses. Serotype-specific neutralization escape mutants in dengue virus E proteins are all located on a surface of domain III, which has been implicated in receptor binding. While antibodies against epitopes in domain I are nonneutralizing in dengue virus, there are neutralizing antibodies that recognize serotype-conserved epitopes in domain II. The mechanism of neutralization for these antibodies is probably inhibition of membrane fusion. Our structure shows that neighboring glycans on the viral surface are spaced widely enough (at least 32 Å) that they can interact with multiple carbohydrate recognition domains on oligomeric lectins such as DC-SIGN, ensuring maximum affinity for these putative receptors.

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Profiles of antibody-dependent enhancement of dengue virus type 2 infection

Cited by 61 publications

References 9 publications

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice

Human Monoclonal Antibodies against West Nile Virus Induced by Natural Infection Neutralize at a Postattachment Step

Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein

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