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

Frederic Sorgeloos, Sarah L. Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate J Heesom, Nicolas Locker, Ian Goodfellow

Research output: Contribution to journalArticle (Academic Journal)peer-review

24 Citations (Scopus)
294 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)S215-S229
Number of pages15
JournalMolecular and Cellular Proteomics
Volume16
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Fingerprint

Dive into the research topics of 'Norovirus-Mediated Modification of the Translational Landscape via Virus and Host-Induced Cleavage of Translation Initiation Factors'. Together they form a unique fingerprint.

Cite this