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Mol Cell Proteomics. 2017 Apr;16(4 suppl 1):S215-S229. doi: 10.1074/mcp.M116.062448. Epub 2017 Jan 13.

Norovirus-Mediated Modification of the Translational Landscape via Virus and Host-Induced Cleavage of Translation Initiation Factors.

Author information

1
From the ‡Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, UK; ee273@cam.ac.uk ig299@cam.ac.uk.
2
From the ‡Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, UK.
3
§Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
4
¶Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX.
5
‖Proteomics facility, School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, UK.
6
**Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, UK.

Abstract

Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded viral protein genome-linked (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 analyze 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.

PMID:
28087593
PMCID:
PMC5393397
DOI:
10.1074/mcp.M116.062448
[Indexed for MEDLINE]
Free PMC Article

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