RIG-I-like receptors (RLRs) are a family of structurally and functionally related cytoplasmic nucleic acid sensors with selectivity for RNA molecules, and are critical for host antiviral responses [1]. These exist in contrast to the endosomally restricted Toll-like receptors for nucleic acids.

The three human RLRs are RIG-1 (DDX58), MDA5 (IFIH1) and LGP2 (DHX58). RLR signaling activates the inflammatory transcription factors (IRFs), AP-1, and NFκB and initiates a type I interferon response [2-3].

RIG-1 and MDA5 contain a core DExD/H box RNA helicase and two caspase recruiting domain (CARD)-like motifs. The dsRNA binds at the helicase domain, and the CARD domains recruit caspases and other signalling complex components (e.g. mitochondrial antiviral signaling (MAVS)) required to relay the signal. Despite their structural similarity, RIG-1 and MDA5 detect distinct viral species [4-5], although there is some overlap. LGP2 does not contain CARD domains and acts predominantly as a negative feedback regulator of RIG-I and MDA5 by binding and sequestering dsRNA.

1. Ahlers LR, Goodman AG. (2016) Nucleic acid sensing and innate immunity: signaling pathways controlling viral pathogenesis and autoimmunity. Curr Clin Microbiol Rep, 3 (3): 132-141. [PMID:27857881]

2. Bruns AM, Horvath CM. (2014) Antiviral RNA recognition and assembly by RLR family innate immune sensors. Cytokine Growth Factor Rev, 25 (5): 507-12. [PMID:25081315]

3. Bryant CE, Orr S, Ferguson B, Symmons MF, Boyle JP, Monie TP. (2015) International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease. Pharmacol Rev, 67 (2): 462-504. [PMID:25829385]

4. Kawai T, Akira S. (2007) Antiviral signaling through pattern recognition receptors. J Biochem, 141 (2): 137-45. [PMID:17190786]

5. Liu Y, Olagnier D, Lin R. (2016) Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity. Front Immunol, 7: 662. [PMID:28096803]