Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation

Myra Hosmillo; Jia Lu; Michael R. McAllaster; James B. Eaglesham; Xinjie Wang; Edward Emmott; Patricia Domingues; Yasmin Chaudhry; Timothy J Fitzmaurice; Matthew K.H. Tung; Marc Panas; Gerald McInerney; Nicholas Locker; Craig B. Willen; Ian Goodfellow

We have previously found that norovirus infection leads to a translation bias whereby 462 cellular mRNAs induced in response to infection are inefficiently translated (Emmott 463 et al., 2017) . Our data suggested that this modification of host cell translation was at 464 least partially driven by the ability of the viral NS6 protease to cleave PABP and the 465 induction of apoptosis which results in cleavage of cellular translation initiation 466 factors (Emmott et al., 2017) . Furthermore, we have more recently shown that the 467 ability of the protease to cleave PABP and other substrates is controlled by 468 polyprotein processing and interactions with other viral proteins (Emmott et al., 469 2019) . Recent work would agree with our observations and confirms that the 470 translational bias is not driven by phosphorylation of eIF2α and that activation of 471 GCN2 leads to the phosphorylation of eIF2α (Brocard et al., 2018) . We note however 472 that others have suggested that NS3 may contribute to translational shut off (Fritzlar 473 et al., 2019) , with the caveat that this observation was made outside of the context of 474 . CC-BY-NC 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/571455 doi: bioRxiv preprint 22 infected cells and using overexpressed tagged proteins.