Cell Host Microbe 2018 09 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.
Neutralizing Antibodies Act on the Outer Leaflet of the Plasma Membrane to Block CHIKV Budding
We have submitted your request - we will update you on status within the next 24 hours.
Sign up for further access to Scientific Publications and Authors!
What are PubFacts Points?
PubFacts points are rewards to PubFacts members, which allow you to better promote your profile and articles throughout PubFacts.com
How do I earn PubFacts Points?
Each member is given 50 PubFacts points upon signing up. You can earn additional points by completing 100% of your profile, creating and participating in discussions, and sharing other members research.
What can I do with PubFacts Points?
Currently, you can use PubFacts Points to promote and increase readership of your articles.