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

The detailed proteomic analysis of the viral replication and translation complexes 389 formed during MNV infection (Fig 2) resulted in the identification of several host 390 factors with previously identified roles in the MNV life cycle. We focused our efforts 391 on G3BP1 as it was identified in all three approaches and was also identified in a 392 CRISPR screen published during this study . Furthermore, we 393 have previously shown that feline calicivirus (FCV), a relative of noroviruses within 394 the Vesivirus genus, cleaves G3BP1 to inhibit stress granule formation (Humoud et 395 al., 2016) . In contrast, MNV infection does not result in G3BP1 cleavage and instead 396 forms cytoplasmic foci the composition of which is distinct from canonical stress 397 granules (Brocard et al., 2018) . 398 G3BP1 is one member of a group of G3BP proteins (Ras-GTPase-activating protein 399 (SH3 domain)-binding proteins), referred to as Rasputin in insects, that possess 400 . CC-BY-NC 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 RNA binding activity and have multiple cellular functions including the regulation of 401 RNA stability and translation in response to stress. Originally identified as a protein 402 that interacted with Ras-GTPase activating protein (RasGAP), more than two 403 decades of research have significantly expanded our knowledge of the 404 multifunctional role in cellular processes. It is now well accepted that G3BPs play a 405 role in cancer cell survival, cancer metastasis and invasion, processing of specific 406 miRNAs and stress granule formation (Reviewed in (Alam and Kennedy, 2019) . 407