Hepatitis C Virus Exploitation of Processing Bodies

Abstract

During infection, positive-strand RNA viruses subvert cellular machinery involved in RNA metabolism to translate viral proteins and replicate viral genomes to avoid or disable the host defense mechanisms. Cytoplasmic RNA granules modulate the stabilities of cellular and viral RNAs. Understanding how hepatitis C virus and other flaviviruses interact with the host machinery required for protein synthesis, localization, and degradation of mRNAs is important for elucidating how these processes occur in both virus-infected and uninfected cells.

FIG 1

Cytoplasmic RNA granules in uninfected and HCV-infected cells. Different dynamic systems modulate the life of a cellular mRNA. Activation of the translation initiation complex determines whether the mRNA is translated or whether, following stress and phosphorylation of α subunit of eukaryotic initiation factor 2 (eIF2α) and association with different RNA-binding proteins (RBPs), the mRNA is stored in stress granules. Processing bodies (P-bodies) are cytoplasmic RNA-protein structures involved in mRNA storage and decay, microRNA-induced gene silencing (miRISC), and mRNA surveillance through the interaction with stress granules. The balance of these pathways is, however, perturbed when the cell is infected with HCV, which subverts and causes the relocalization of P-body and stress granule components. During HCV infection, different components of stress granules and P-bodies relocalize to lipid droplets, the site of virion assembly.