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Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors

Emmott, E, Sorgeloos, F, Caddy, SL, Vashist, S, Sosnovtsev, S, Lloyd, R, Heesom, K, Locker, Nicolas and Goodfellow, I (2017) Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors Molecular and Cellular Proteomics, 16. S215-S229.

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Abstract

Noroviruses produce viral RNAs lacking a 5’ cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex. The suppression of host ISG translation correlates with the activity of the viral protease (NS6) and the activation of cellular caspases leading to the establishment of an apoptotic environment. These results indicate that noroviruses exploit the differences between viral VPg-dependent and cellular cap-dependent translation in order to diminish the host response to infection.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Emmott, EUNSPECIFIEDUNSPECIFIED
Sorgeloos, FUNSPECIFIEDUNSPECIFIED
Caddy, SLUNSPECIFIEDUNSPECIFIED
Vashist, SUNSPECIFIEDUNSPECIFIED
Sosnovtsev, SUNSPECIFIEDUNSPECIFIED
Lloyd, RUNSPECIFIEDUNSPECIFIED
Heesom, KUNSPECIFIEDUNSPECIFIED
Locker, NicolasN.Locker@surrey.ac.ukUNSPECIFIED
Goodfellow, IUNSPECIFIEDUNSPECIFIED
Date : 13 January 2017
Identification Number : 10.1074/mcp.M116.062448
Copyright Disclaimer : Copyright 2017 American Society for Biochemistry and Molecular Biology Published under a Creative Commons: CC-BY license
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 14 Feb 2017 14:54
Last Modified : 07 Jul 2017 10:39
URI: http://epubs.surrey.ac.uk/id/eprint/813531

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