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dc.contributor.authorEmmott, Edwarden
dc.contributor.authorSorgeloos, Fredericen
dc.contributor.authorCaddy, Sarahen
dc.contributor.authorVashist, Sen
dc.contributor.authorSosnovtsev, Sen
dc.contributor.authorLloyd, Ren
dc.contributor.authorHeesom, Ken
dc.contributor.authorLocker, Nen
dc.contributor.authorGoodfellow, Ianen
dc.date.accessioned2017-03-29T15:20:10Z
dc.date.available2017-03-29T15:20:10Z
dc.date.issued2017-01-13en
dc.identifier.issn1535-9476
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263331
dc.description.abstractNoroviruses 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.
dc.description.sponsorshipThis 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.
dc.languageengen
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.subjectapoptosis*en
dc.subjectcalicivirusen
dc.subjectcell biology*en
dc.subjectmass Spectrometryen
dc.subjectnorovirusen
dc.subjectPABPen
dc.subjectproteases*en
dc.subjectSILACen
dc.subjecttranslation*en
dc.subjectvirusesen
dc.titleNorovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factorsen
dc.typeArticle
prism.publicationDate2017en
prism.publicationNameMolecular & Cellular Proteomicsen
dc.identifier.doi10.17863/CAM.8667
dcterms.dateAccepted2017-01-13en
rioxxterms.versionofrecord10.1074/mcp.M116.062448en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-01-13en
dc.contributor.orcidSorgeloos, Frederic [0000-0002-6492-8524]
dc.contributor.orcidCaddy, Sarah [0000-0002-9790-7420]
dc.contributor.orcidGoodfellow, Ian [0000-0002-9483-510X]
dc.identifier.eissn1535-9484
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/N001176/1)
pubs.funder-project-idWellcome Trust (097997/Z/11/Z)
pubs.funder-project-idWellcome Trust (101602/Z/13/Z)


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