Fusion-active glycoprotein G mediates the cytotoxicity of vesicular stomatitis virus M mutants lacking host shut-off activity

The Journal of General Virology
Markus HoffmannGert Zimmer

Abstract

The cytopathogenicity of vesicular stomatitis virus (VSV) has been attributed mainly to the host shut-off activity of the viral matrix (M) protein, which inhibits both nuclear transcription and nucleocytoplasmic RNA transport, thereby effectively suppressing the synthesis of type I interferon (IFN). The M protein from persistently VSV-infected cells was shown to harbour characteristic amino acid substitutions (M51R, V221F and S226R) implicated in IFN induction. This study demonstrates that infection of human fibroblasts with recombinant VSV containing the M51R substitution resulted in IFN induction, whereas neither the V221F nor the S226R substitution effected an IFN-inducing phenotype. Only when V221F was combined with S226R were the host shut-off activity of the M protein abolished and IFN induced, independently of M51R. The M33A substitution, previously implicated in VSV cytotoxicity, did not affect host shut-off activity. M-mutant VSV containing all four amino acid substitutions retained cytotoxic properties in both Vero cells and IFN-competent primary fibroblasts. Infected-cell death was associated with the formation of giant polynucleated cells, suggesting that the fusion activity of the VSV G protein was involved. Accord...Continue Reading

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Citations

Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kevin T BeierConstance L Cepko
Nov 11, 2011·Journal of Virology·Matthias LinigerNicolas Ruggli
Jan 31, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alexander MuikDorothee von Laer
Sep 22, 2012·Veterinary Microbiology·Bettina ZimmerGert Zimmer
Apr 3, 2012·Gastroenterology·Sibylle HaidThomas Pietschmann
Mar 13, 2015·Scientific Reports·Khaled S SanberYasuhiro Takeuchi
Mar 12, 2011·The Journal of Gene Medicine·Luciene LopesMary K Collins
Oct 12, 2012·The Journal of General Virology·Eric Hastie, Valery Z Grdzelishvili
Jun 26, 2013·Virus Research·Eric HastieValery Z Grdzelishvili
Mar 3, 2018·Viruses·Janine KimpelDorothee von Laer
Mar 24, 2017·Journal of Virology·Marc SchwenekerJürgen Hausmann
Mar 5, 2013·Médecine sciences : M/S·Valérie JanelleAlain Lamarre
Jan 1, 2021·Vaccines·Lydia RieplerJanine Kimpel
Sep 6, 2018·Molecular Therapy. Methods & Clinical Development·Maha TijaniYasuhiro Takeuchi

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