Conformational Changes in Sindbis Virus E1 Glycoprotein Induced by Monoclonal Antibody Binding

Clegg, J. C. S.; Chañas, A. C.; Gould, Ernest A.

doi:10.1099/0022-1317-64-5-1121

Cited by 28 publications

(15 citation statements)

References 20 publications

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“…4C). Similar epitope-specific antibody-mediated structural changes have also been described for other viruses (62)(63)(64). In the case of HIV, they were implicated in the enhanced antigenicity of neutralizing antigenic sites involving the V3 loop of gp 120 after immunization with ICs containing the HIV gp 120 (28,65).…”

Section: Discussionsupporting

confidence: 60%

Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

Tsouchnikas

Zlatkovic

Jarmer

et al. 2015

J Virol

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The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as an immunogen. TBE virus occurs in Europe and Asia and-together with the yellow fever, dengue, West Nile, and Japanese encephalitis viruses-represents one of the major human-pathogenic flaviviruses. Mice were immunized with a dimeric soluble form of E (sE) alone or in complex with monoclonal antibodies specific for each of the three domains of E, and the antibody response induced by these ICs was compared to that seen after immunization with sE alone. Immunoassays using recombinant domains and domain combinations of TBE virus sE as well as the distantly related West Nile virus sE allowed the dissection and quantification of antibody subsets present in postimmunization sera, thus generating fine-specificity patterns of the polyclonal responses. There were substantially different responses with two of the ICs, and the differences could be mechanistically related to (i) epitope shielding and (ii) antibody-mediated structural changes leading to dissociation of the sE dimer. The phenomena described may also be relevant for polyclonal responses upon secondary infections and/or booster immunizations and may affect antibody responses in an individual-specific way. IMPORTANCEInfections with flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis (TBE) viruses pose substantial public health problems in different parts of the world. Antibodies to viral envelope protein E induced by natural infection or vaccination were shown to confer protection from disease. Such antibodies can target different epitopes in E protein, and the fine specificities of polyclonal responses can differ between individuals. We conducted a mouse immunization study with TBE E protein alone or complexed to monoclonal antibodies specific for each of the three protein domains. We demonstrated that phenomena such as epitope shielding and antibody-induced structural changes can profoundly influence the fine specificity of antibody responses to the same immunogen. The study thus provided important new information on the potential immunomodulatory role of preexisting antibodies in a flavivirus system that can be relevant for understanding individual-specific factors influencing antibody responses in sequential flavivirus infections and/or immunizations. Several mosquito-and tick-transmitted flaviviruses are important human pathogens and have a substantial public health impact in countries of endemicity (1). These include the yellow fever (YF), dengue (DEN), West Nile (WN), Japanese encephalitis (JE), and tick-borne...

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Section: Discussionsupporting

confidence: 60%

Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

Tsouchnikas

Zlatkovic

Jarmer

et al. 2015

J Virol

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“…To date only the epitopes on the viral surface glycoproteins have been well characterized using monoclonal antibodies (MAbs) (Chanas et al, 1982;Clegg et al, 1983;Davis et al, 1987;Roehrig et al, 1980Roehrig et al, , 1982Stanley et al, 1985;Yamamoto et al, 1985). In order to identify conserved group-reactive antigenic determinants on the NC protein of alphaviruses, MAbs were raised against SF virus.…”

Section: Discussionmentioning

confidence: 99%

Most Alphaviruses Share a Conserved Epitopic Region on Their Nucleocapsid Protein

Greiser‐Wilke¹,

Moennig²,

Kaaden³

et al. 1989

Journal of General Virology

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SUMMARYFourteen hybridoma cell lines secreting antibodies against the Semliki Forest virus nucleocapsid protein were established and employed for identification of conserved epitopes among 27 alphavirus types and subtypes. Using an antibody capture test, the antibodies were found to cross-react to variable degrees with alphaviruses belonging to the Semliki Forest, western encephalitis and eastern encephalitis complexes, as well as Middelburg and Ndumu. None of the antibodies reacted with either Venezuelan equine encephalitis or Barmah Forest virus. Due to their reactivity with Fort Morgan, Y62-33, Whataroa and chikungunya, the monoclonal antibodies were divided into six reactive types. Competition assays showed that the epitopes for all the types were either identical or clustered on a single domain of the nucleocapsid protein.

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“…In three viruses of the WN subgroup, this synergism was also observed using mixtures of anti-JE MAbs from different MAb groups. Some investigators have reported that the binding of antibodies to certain epitopes on virus protein induces conformational changes in distant parts of the molecule and results in the increased avidity of other antibodies (Clegg et al, 1983;Heinz et al, 1984a;Lubeck & Gerhard, 1982). Such conformational changes or steric hindrance of important N sites for virus infection may cause the synergistic N of other flaviviruses.…”

Section: Discussionmentioning

confidence: 99%

Antigenic Comparison of Envelope Protein E between Japanese Encephalitis Virus and Some Other Flaviviruses Using Monoclonal Antibodies

Kimura‐Kuroda

Yasui

1986

Journal of General Virology

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SUMMARYThe antigenic relationships between Japanese encephalitis (JE) virus and several other flaviviruses have been investigated using anti-JE virus monoclonal antibodies (MAbs). Seventeen MAbs directed against envelope protein E of JE virus were characterized and divided into eight MAb groups based on reactivity patterns in haemagglutination inhibition test, neutralization (N) test, ELISA and competitive binding assay with JE virus. The results suggest the existence of at least eight epitopes on the E protein of JE viruses. Analysis of cross-reactivity of the antibodies with several other flaviviruses indicated these findings. (i) JE virus, belonging to West Nile (WN) subgroup, is antigenically closely related to viruses in the same subgroup, i.e. Murray Valley encephalitis (MVE), WN and St. Louis encephalitis (SLE) viruses. Of these three viruses, JE virus has the closest relationship with MVE virus. (ii) WN virusis relatively close to JE virus, whereas SLE virus is the least closely related. (iii) Dengue viruses types 1 and 2, which belong to another subgroup offlaviviruses, show markedly less antigenic homology to JE virus. (iv) One of the critical N sites on the E protein showed JE virus specificity. (v) Some cross-reactive antibodies which did not neutralize JE virus showed low but significant N activity against several other flaviviruses. Mixtures of several MAbs, which showed different reactivity patterns, potentiated the N activity against not only JE virus but also other members of the WN subgroup of flaviviruses, namely MVE, WN and SLE viruses.

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Conformational Changes in Sindbis Virus E1 Glycoprotein Induced by Monoclonal Antibody Binding

Cited by 28 publications

References 20 publications

Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

Most Alphaviruses Share a Conserved Epitopic Region on Their Nucleocapsid Protein

Antigenic Comparison of Envelope Protein E between Japanese Encephalitis Virus and Some Other Flaviviruses Using Monoclonal Antibodies

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