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Feline Calicivirus infection disrupts the assembly of cytoplasmic stress granules and induces G3BP1 cleavage

Humoud, MN, Doyle, N, Royall, E, Willcocks, MM, Sorgeloos, F, van Kuppeveld, F, Roberts, LO, Goodfellow, IG, Langereis, MA and Locker, NS (2016) Feline Calicivirus infection disrupts the assembly of cytoplasmic stress granules and induces G3BP1 cleavage Journal of Virology.

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Abstract

In response to stress such as virus infection, cells can stall translation by storing mRNAs away in cellular compartments called stress granules (SGs). This defence mechanism favours cell survival by limiting the use of energy and nutrients until the stress is resolved. In some cases it may also block viral propagation as viruses are dependent on the host cell resources to produce viral proteins. Human norovirus is a member of the Caliciviridae family responsible for gastroenteritis outbreaks worldwide. Previous studies on caliciviruses have identified mechanisms by which they can usurp the host translational machinery, using the viral protein genome-linked VPg, or regulate host protein synthesis through the MAPK pathway. Herein we examined the effect of feline calicivirus (FCV) infection on SGs accumulation. We show that FCV infection impairs the assembly of SGs despite an increased phosphorylation of eukaryotic initiation factor eIF2α, a hallmark of stress pathway activation. Furthermore SGs did not accumulate in FCV-infected cells that are stressed with arsenite or hydrogen peroxide. FCV infection resulted in the cleavage of the SG-nucleating protein Ras-GTPase activating SH3 domain-binding protein (G3BP1), which is mediated by the viral 3C-like proteinase NS6Pro 38 . Using mutational analysis, we identified the FCV-induced cleavage site within G3BP1, which differs from the poliovirus 3C proteinase cleavage site previously identified. Finally, we showed that NS6Pro 41 -mediated G3BP1 cleavage impairs SGs assembly. In contrast, murine norovirus (MNV) infection did not impact arsenite-induced SG assembly or G3BP1 integrity suggesting that related caliciviruses have distinct effects on the stress response pathway.

Item Type: Article
Subjects : subj_Biosciences
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Humoud, MNUNSPECIFIEDUNSPECIFIED
Doyle, NUNSPECIFIEDUNSPECIFIED
Royall, EUNSPECIFIEDUNSPECIFIED
Willcocks, MMUNSPECIFIEDUNSPECIFIED
Sorgeloos, FUNSPECIFIEDUNSPECIFIED
van Kuppeveld, FUNSPECIFIEDUNSPECIFIED
Roberts, LOUNSPECIFIEDUNSPECIFIED
Goodfellow, IGUNSPECIFIEDUNSPECIFIED
Langereis, MAUNSPECIFIEDUNSPECIFIED
Locker, NSUNSPECIFIEDUNSPECIFIED
Date : 4 November 2016
Funders : BBSRC
Identification Number : 10.1128/JVI.00647-16
Copyright Disclaimer : Copyright © 2016 Humoud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 04 May 2016 13:00
Last Modified : 19 Jul 2016 15:31
URI: http://epubs.surrey.ac.uk/id/eprint/810623

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