Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity

Abstract

Retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) are cytosolic RNA helicases that sense viral RNA and trigger signaling pathways that induce the production of type I interferons (IFNs) and proinflammatory cytokines. RLRs recognize distinct and overlapping sets of viruses, but the mechanisms that dictate this specificity were unknown. A new study now provides evidence for size-based discrimination of double-stranded RNA (dsRNA) by RLRs and suggests how host cells recognize a variety of RNA viruses.

Figure 1.

Nucleic acid sensor molecules induce type I IFN and proinflammatory cytokines. PRRs occupy specific intracellular sites that associate with the niche of different microbial pathogens. MDA5 and RIG-I both serve as cytoplasmic dsRNA receptors but distinguish their ligands in part by size; MDA5 binds to long dsRNA, whereas RIG-I binds short dsRNA. Among the TLRs, TLR3 recognizes dsRNA, TLR7/8 recognizes endosomal ssRNA, and TLR9 binds to endosomal CpG DNA. PRR activation initiates downstream signaling that in turn activates transcription factors, including IRF-3, IRF-7, and NF-κB. The resulting expression of type I IFNs, proinflammatory cytokines, and IFN-stimulated genes affect the innate immune response to confer pathogen resistance and enhance the adaptive immune response to infection.