RT Journal Article
SR Electronic
T1 Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 060772
DO 10.1101/060772
A1 Edward Emmott
A1 Frederic Sorgeloos
A1 Sarah L. Caddy
A1 Surender Vashist
A1 Stanislav Sosnovtsev
A1 Richard Lloyd
A1 Kate Heesom
A1 Ian Goodfellow
YR 2016
UL http://biorxiv.org/content/early/2016/06/26/060772.abstract
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.