Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane.

Authors:
Jing Jin
Jing Jin
School of Pharmaceutical Sciences
China
Michael B Sherman
Michael B Sherman
University of Texas Medical Branch
United States
Stella Y Sun
Stella Y Sun
National University of Singapore
Cynthia S Goldsmith
Cynthia S Goldsmith
National Kaohsiung Normal University
Taiwan

Cell Host Microbe 2018 Sep 23;24(3):417-428.e5. Epub 2018 Aug 23.

Blood Systems Research Institute, San Francisco, CA 94118, USA; Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

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.

Abstract Video

Neutralizing Antibodies Act on the Outer Leaflet of the Plasma Membrane to Block CHIKV Budding


Source: Cell Press

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Source
http://dx.doi.org/10.1016/j.chom.2018.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137268PMC

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September 2018
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