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TitleNeutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane.
Journal, issue, pagesCell Host Microbe, Vol. 24, Issue 3, Page 417-428.e5, Year 2018
Publish dateSep 12, 2018
AuthorsJing Jin / Jesús G Galaz-Montoya / Michael B Sherman / Stella Y Sun / Cynthia S Goldsmith / Eileen T O'Toole / Larry Ackerman / Lars-Anders Carlson / Scott C Weaver / Wah Chiu / Graham Simmons /
PubMed AbstractNeutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune ...Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune cells to activate antiviral responses. We describe a mechanism by which NAbs inhibit chikungunya virus (CHIKV), the most common alphavirus infecting humans, by preventing virus budding from infected human cells and activating IgG-specific Fcγ receptors. NAbs bind to CHIKV glycoproteins on the infected cell surface and induce glycoprotein coalescence, preventing budding of nascent virions and leaving structurally heterogeneous nucleocapsids arrested in the cytosol. Furthermore, NAbs induce clustering of CHIKV replication spherules at sites of budding blockage. Functionally, these densely packed glycoprotein-NAb complexes on infected cells activate Fcγ receptors, inducing a strong, antibody-dependent, cell-mediated cytotoxicity response from immune effector cells. Our findings describe a triply functional antiviral pathway for NAbs that might be broadly applicable across virus-host systems, suggesting avenues for therapeutic innovation through antibody design.
External linksCell Host Microbe / PubMed:30146390 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution34.0 - 36.0 Å
Structure data

EMDB-7513:
Subtomogram average of mature CHIKV virion budded from human cells
Method: EM (subtomogram averaging) / Resolution: 34.0 Å

EMDB-7515:
Subtomogram averages of budding-arrested nucleocapsid-like particles (NCLPs) inside CHIKV-infected human cells.
Method: EM (subtomogram averaging) / Resolution: 36.0 Å

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