RIG-I-like Receptor

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are a family of cytosolic pattern recognition receptors (PRRs) that recognize viral RNA and result in immunological response. RLRs include RIG-I (retinoic acid-inducible gene I), MDA5 (melanoma differentiation associated factor 5), and LGP2 (laboratory of genetics and physiology 2). They share a number of structural similarities including their organization into three distinct domains: 1) An N-terminal region consisting of tandem caspase activation and recruitment domains (CARD); 2) A central DExD/H box RNA helicase domain with the capacity to hydrolyze ATP and to bind RNA; 3) A repressor domain (RD) embedded within the carboxy-terminal domain (CTD). LGP2 lacks the CARDs and is widely thought to function as a regulator of RIG-I and MDA5. Upon RNA binding and oligomerization, RLRs interact with mitochondrial antiviral-signalling protein (MAVS) via CARD–CARD interactions. Activated MAVS then activates TANK-binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylates IRF3 and IRF7; these, together with nuclear factor-κB (NF-κB), then induce transcription of the genes encoding type I interferons and other antiviral or immunoregulatory genes.