Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors
Molecular & Cellular Proteomics
American Society for Biochemistry and Molecular Biology
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Emmott, E., Sorgeloos, F., Caddy, S., Vashist, S., Sosnovtsev, S., Lloyd, R., Heesom, K., et al. (2017). Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors. Molecular & Cellular Proteomics https://doi.org/10.1074/mcp.M116.062448
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.
apoptosis*, calicivirus, cell biology*, mass Spectrometry, norovirus, PABP, proteases*, SILAC, translation*, viruses
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.
Wellcome Trust (097997/Z/11/Z)
Wellcome Trust (101602/Z/13/Z)
External DOI: https://doi.org/10.1074/mcp.M116.062448
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263331