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

Poltronieri, Palmiro; Sun, Binlian; Mallardo, Massimo

Different viruses exploit the binding to protein scaffolds to avoid SG formation or to assemble their RNA into SGs devoid of cellular RNA, thus exploiting the transcriptional machinery for their own means [64] . In RNA viruses, the knowledge has increased recently, especially focusing on HCV infected cells, where SG and P-body components are relocalised to the periphery of lipid droplets, and an oscillation between SG assembly and disassembly is observed upon interferon I treatment, depending on the inhibition of PKR by the eIF2 phosphatase GADD34 [65] . West Nile Virus (WNV) inhibits SG formation by scavenging Reactive Oxygen Species (ROS), and also relocalising the SG scaffolding proteins into perinuclear foci where WNV replication occurs by exploiting cell translation machinery. HIV-1 blocks SG assembly in vitro and ex vivo in patient samples. Gag has an important role in inhibition of SG, dependent on the interaction between host factors EIF2 and G3BP1. Influenza A virus (IAV) proteins can block SG formation: IAV polymerase complexes function in the nuclei of infected cells, generating mRNAs with a 5' cap and polyA-tail that are transferred into the cytoplasm for translation. Non-structural protein 1 (NS1) inactivates PKR, preventing eIF2 phoshorylation; nucleoprotein (NP) inhibits SG formation through eIF independent mechanisms; host-shutoff protein polymerase-acidic protein-X (PA-X) is essential to block SG formation. Measles virus infection progresses through the synthesis of 5'-copyback defective-interfering RNA (DI-RNAs), that are complementary in the 5' and 3' termini, forming double stranded RNAs, efficient in activation of PKR and PKR signaling. Downstream to this event, measles protein C is required for alleviation of SG translation inhibition, while A-to-C mutation events dependent on ADAR modify the virus genome. In picornaviruses, such as enteroviruses, proteinases have been shown involved in disassembly of SG, while in kobuviruses other factors, such as a small leader peptide, are important in SG inhibition.