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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Emmott, E 
Sorgeloos, Frederic  ORCID logo  https://orcid.org/0000-0002-6492-8524
Caddy, SL 
Vashist, S 
Sosnovtsev, S 

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.

Description

Keywords

apoptosis*, calicivirus, cell biology*, mass Spectrometry, norovirus, PABP, proteases*, SILAC, translation*, viruses

Journal Title

Molecular & Cellular Proteomics

Conference Name

Journal ISSN

1535-9476
1535-9484

Volume Title

Publisher

American Society for Biochemistry and Molecular Biology
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/N001176/1)
Wellcome Trust (097997/Z/11/Z)
Wellcome Trust (101602/Z/13/Z)
This work was supported by grants from the Wellcome Trust (097997/Z/11/Z, 101602/Z/13/Z) and BBSRC (Refs: BB/N001176/1 and BB/K002465/1) to IG, and an equipment grant to KH, IG (and others) from the Wellcome Trust (104914/Z/14/Z). RL is supported by a grant from the National Institutes for Health of the United States of America (AI50237). NL is supported by a BBSRC grant (BB/I01232X/1). IG is a Wellcome Senior Fellow. This work was also supported by the Intramural Research Program of the NIH, NIAID.