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Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane
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2018 (engelsk)Inngår i: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 24, nr 3, s. 417-+Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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 Fc gamma 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 Fc gamma 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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Cell Press , 2018. Vol. 24, nr 3, s. 417-+
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-152990DOI: 10.1016/j.chom.2018.07.018ISI: 000446887200013PubMedID: 30146390OAI: oai:DiVA.org:umu-152990DiVA, id: diva2:1260181
Forskningsfinansiär
NIH (National Institute of Health), R01 AI119056NIH (National Institute of Health), P41GM103832NIH (National Institute of Health), R24AI120942Tilgjengelig fra: 2018-11-01 Laget: 2018-11-01 Sist oppdatert: 2018-11-01bibliografisk kontrollert

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