Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors
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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 | ||||||||||||||||||||||||||||||
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| Subjects : | Biosciences and Medicine | ||||||||||||||||||||||||||||||
| Divisions : | Faculty of Health and Medical Sciences > School of Biosciences and Medicine | ||||||||||||||||||||||||||||||
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| Date : | 13 January 2017 | ||||||||||||||||||||||||||||||
| DOI : | 10.1074/mcp.M116.062448 | ||||||||||||||||||||||||||||||
| Copyright Disclaimer : | Copyright 2017 American Society for Biochemistry and Molecular Biology Published under a Creative Commons: CC-BY license | ||||||||||||||||||||||||||||||
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| Depositing User : | Symplectic Elements | ||||||||||||||||||||||||||||||
| Date Deposited : | 14 Feb 2017 14:54 | ||||||||||||||||||||||||||||||
| Last Modified : | 16 Jan 2019 17:12 | ||||||||||||||||||||||||||||||
| URI: | http://epubs.surrey.ac.uk/id/eprint/813531 |
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