Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane

Cell Host & Microbe
Jing JinGraham Simmons

Abstract

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.

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Citations

Apr 7, 2020·Expert Opinion on Therapeutic Patents·Ritu Ghildiyal, Reema Gabrani
Sep 5, 2019·Nature Reviews. Rheumatology·Andreas Suhrbier
Jul 24, 2020·Journal of Virology·Uranan TumkositAtsushi Tanaka
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Mar 31, 2019·Viruses·Jing Jin, Graham Simmons
May 16, 2020·Frontiers in Immunology·Priyanshu SrivastavaSujatha Sunil
Feb 11, 2021·Memórias do Instituto Oswaldo Cruz·Debora Ferreira Barreto-VieiraOrtrud Monika Barth
Nov 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jane X YehDiane E Griffin
Oct 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Qun Fei ZhouShee-Mei Lok
Sep 28, 2020·Cell·Hangping YaoSai Li
Apr 8, 2021·Cell Reports·James T EarnestMichael S Diamond
Jan 15, 2021·Annual Review of Physical Chemistry·Peter D Dahlberg, W E Moerner

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