Genetic Inactivation of COPI Coatomer Separately Inhibits Vesicular Stomatitis Virus Entry and Gene Expression
Author
Cureton, David K.
Burdeinick-Kerr, Rebeca
Whelan, Sean J.
Published Version
https://doi.org/10.1128/JVI.05810-11Metadata
Show full item recordCitation
Cureton, D. K., R. Burdeinick-Kerr, and S. P. J. Whelan. 2011. “Genetic Inactivation of COPI Coatomer Separately Inhibits Vesicular Stomatitis Virus Entry and Gene Expression.” Journal of Virology 86 (2): 655–66. https://doi.org/10.1128/jvi.05810-11.Abstract
Viruses coopt cellular membrane transport to invade cells, establish intracellular sites of replication, and release progeny virions. Recent genome-wide RNA interference (RNAi) screens revealed that genetically divergent viruses require biosynthetic membrane transport by the COPI coatomer complex for efficient replication. Here we found that disrupting COPI function by RNAi inhibited an early stage of vesicular stomatitis virus (VSV) replication. To dissect which replication stage(s) was affected by coatomer inactivation, we used visual and biochemical assays to independently measure the efficiency of viral entry and gene expression in hamster (ldlF) cells depleted of the temperature-sensitive epsilon-COP subunit. We show that epsilon-COP depletion for 12 h caused a primary block to virus internalization and a secondary defect in viral gene expression. Using brefeldin A (BFA), a chemical inhibitor of COPI function, we demonstrate that short-term (1-h) BFA treatments inhibit VSV gene expression, while only long-term (12-h) treatments block virus entry. We conclude that prolonged coatomer inactivation perturbs cellular endocytic transport and thereby indirectly impairs VSV entry. Our results offer an explanation of why COPI coatomer is frequently identified in screens for cellular factors that support cell invasion by microbial pathogens.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483484
Collections
- HMS Scholarly Articles [17714]
Contact administrator regarding this item (to report mistakes or request changes)