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

indirectly promotes the recruitment of 40S ribosomal subunits to VPg-driven 432 translation complexes. The RGG motif of G3BP1 is known to be essential for the 433 association between G3BP1 and 40S subunits as well as the ability to from stress 434 granules, whereas data would suggest that the RRM may play a regulatory role 435 (Kedersha et al., 2016) . These domains were also required for the function of G3BP1 436 in the norovirus life cycle (Fig 6) confirming that the G3BP1 association with 40S is 437 important for its role in promoting norovirus VPg-dependent translation. Importantly, 438 RGG domains are known to have many functions (Thandapani et al., 2013) and 439 therefore in the context of G3BP1 function in the norovirus life cycle, may also 440 contribute to unknown interactions that promote norovirus translation. Previous work 441 on alphaviruses have shown that G3BP1 is sequestered by binding to the nsP3 442 protein (Panas et al., 2012; 2015) . Furthermore, this interaction occurs via an 443 FGDF motif also found in other viral proteins including the ICP8 protein of herpes 444 simplex virus (Panas et al., 2015) . While the MNV VPg protein has a similar motif 445 FGDGF (Fig 1A) , this motif is not conserved in the GI Norwalk virus VPg protein. 446