RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load

Poltronieri, Palmiro; Sun, Binlian; Mallardo, Massimo

It was shown that viral life cycle within cells involves hijacking cellular processes and nuclear targeting. This is also at the base of redistribution of translation machinery during the stress response involving the formation of stress granules, processing bodies (P-bodies, PB), and perinuclear paraspeckles. During oxidative stress, arsenite, or by phosphorylation of eIF2 , cells undergo a translation arrest, stalling the RNAs in the form of ternary complexes that include eukaryotic initiation factor 2 (eIF2)/GTP/Met-tRNA. These stress granules, containing the RNA to be translated, have a role in spatial and temporal inhibition of mRNAs, until resolving the stress for processing the mRNAs, or degrading it in case of non recovery from the stress. Stress granules are formed by a nucleation process that involves several principal factors, such as the RNA decay factor G3BP, which prevents the localisation of ribosome and initiation factors in silenced SG foci, the translational suppressor TIA1, TIAR, Caprin1, USP10, DDX6 (Rck/p54), DDX3 helicase, poly-A binding protein PAPB and Lsm1. Additionally, SGs contain enzymes of the RNA silencing pathway, such as Argoanute-2, trans-acting factors, Hsp90 complexes and RNA binding proteins, found at the site of small RNA-mediated repression of RNA targets [63] .