PT  - JOURNAL ARTICLE
AU  - Myra Hosmillo
AU  - Jia Lu
AU  - Michael R. McAllaster
AU  - James B. Eaglesham
AU  - Xinjie Wang
AU  - Edward Emmott
AU  - Patricia Domingues
AU  - Yasmin Chaudhry
AU  - Timothy J Fitzmaurice
AU  - Matthew K.H. Tung
AU  - Marc Panas
AU  - Gerald McInerney
AU  - Nicholas Locker
AU  - Craig B. Willen
AU  - Ian Goodfellow
TI  - Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation
AID  - 10.1101/571455
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 571455
4099  - http://biorxiv.org/content/early/2019/03/08/571455.short
4100  - http://biorxiv.org/content/early/2019/03/08/571455.full
AB  - Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the Norovirus genus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating 40S recruitment. Our data suggest that G3BP1 functions by providing viral RNA a competitive advantage over capped cellular RNAs, uncovering a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifying the first host factor with pan-norovirus pro-viral activity.