PT  - JOURNAL ARTICLE
AU  - Edward Emmott
AU  - Frederic Sorgeloos
AU  - Sarah L. Caddy
AU  - Surender Vashist
AU  - Stanislav Sosnovtsev
AU  - Richard Lloyd
AU  - Kate Heesom
AU  - Ian Goodfellow
TI  - Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors
AID  - 10.1101/060772
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 060772
4099  - http://biorxiv.org/content/early/2016/06/26/060772.short
4100  - http://biorxiv.org/content/early/2016/06/26/060772.full
AB  - 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. Using a novel mass spectrometry approach we 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.