Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1002390
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dc.titleChikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants
dc.contributor.authorLee C.Y.
dc.contributor.authorKam Y.-W.
dc.contributor.authorFric J.
dc.contributor.authorMalleret B.
dc.contributor.authorKoh E.G.L.
dc.contributor.authorPrakash C.
dc.contributor.authorHuang W.
dc.contributor.authorLee W.W.L.
dc.contributor.authorLin C.
dc.contributor.authorLin R.T.P.
dc.contributor.authorRenia L.
dc.contributor.authorWang C.-I.
dc.contributor.authorNg L.F.P.
dc.contributor.authorWarter L.
dc.date.accessioned2019-11-06T09:30:56Z
dc.date.available2019-11-06T09:30:56Z
dc.date.issued2011
dc.identifier.citationLee C.Y., Kam Y.-W., Fric J., Malleret B., Koh E.G.L., Prakash C., Huang W., Lee W.W.L., Lin C., Lin R.T.P., Renia L., Wang C.-I., Ng L.F.P., Warter L. (2011). Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants. PLoS Pathogens 7 (12) : e1002390. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1002390
dc.identifier.issn15537366
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161646
dc.description.abstractChikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis. © 2011 Lee et al.
dc.sourceUnpaywall 20191101
dc.subjectneutralizing antibody
dc.subjectimmunoglobulin M
dc.subjectmonoclonal antibody
dc.subjectneutralizing antibody
dc.subjectvirus antibody
dc.subjectvirus antigen
dc.subjectvirus protein
dc.subjectarticle
dc.subjectChikungunya alphavirus
dc.subjectcontrolled study
dc.subjectnonhuman
dc.subjectvirus cell interaction
dc.subjectvirus mutation
dc.subjectvirus neutralization
dc.subjectvirus resistance
dc.subjectvirus transmission
dc.subjectAlphavirus infection
dc.subjectanimal
dc.subjectcell strain HEK293
dc.subjectchronic disease
dc.subjectdisease transmission
dc.subjectgenetics
dc.subjecthuman
dc.subjectimmune evasion
dc.subjectimmunology
dc.subjectmouse
dc.subjectmouse mutant
dc.subjectmutation
dc.subjectpathogenicity
dc.subjectprotein secondary structure
dc.subjectprotein tertiary structure
dc.subjectAlphavirus
dc.subjectAnimalia
dc.subjectChikungunya virus
dc.subjectPrimates
dc.subjectAlphavirus Infections
dc.subjectAnimals
dc.subjectAntibodies, Monoclonal
dc.subjectAntibodies, Neutralizing
dc.subjectAntibodies, Viral
dc.subjectAntigens, Viral
dc.subjectChikungunya virus
dc.subjectChronic Disease
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectImmune Evasion
dc.subjectImmunoglobulin M
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMutation
dc.subjectProtein Structure, Secondary
dc.subjectProtein Structure, Tertiary
dc.subjectViral Proteins
dc.typeArticle
dc.contributor.departmentLIFE SCIENCES INSTITUTE
dc.contributor.departmentDEPT OF PATHOLOGY
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.description.doi10.1371/journal.ppat.1002390
dc.description.sourcetitlePLoS Pathogens
dc.description.volume7
dc.description.issue12
dc.description.pagee1002390
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