Figure 1.

Innate cytosolic sensors of viral RNA. Upon infection, RNA viruses access the cytosol, where they can be amplified by viral RNA-dependent RNA polymerases. Once in the cytosol, viral RNA can be recognized by several innate sensors of RNA, including: Protein Kinase R (PKR); RIG-I-like receptors (RLRs), as well as IFITs 1 and 5. PKR recognizes double-stranded (ds) RNA as well as 5′ triphosphate-containing single-stranded (ss) RNAs. Activation of PKR leads to type I IFN signaling mediated by NF-κB as well as phosphorylation of eIF2α leading to inhibition of cap-dependent translation. The RLRs, including RIG-I, MDA5 and LGP2, recognize primarily dsRNA or highly structured ssRNAs, and at least RIG-I and MDA5 have been demonstrated to be activated by 5′ triphosphate RNA, while the precise substrate for LGP2 has not been defined. Recognition of viral RNA by RLRs leads to recruitment of RIG-I and MDA-5 to the adaptor protein MAVS, which initiates downstream type I IFN signaling through NF-κB and IRF3/7. Finally, IFITs 1 and 5 have been demonstrated to interact with 5′ triphosphate containing ssRNAs leading to viral RNA sequestration and translational inhibition.