RIG-I-like receptor signaling pathway (RLR signaling pathway)

The RIG-I-like receptor signaling pathway is a key component of the innate immune system that detects cytosolic viral RNAs through pattern recognition receptors including RIG-I (retinoic acid-inducible gene I, also known as DDX58), MDA5 (melanoma differentiation-associated protein 5), and LGP2. These receptors feature a DExD/H-box RNA helicase domain for RNA binding and ATPase activity, with RIG-I and MDA5 containing N-terminal CARD domains that interact with the adapter protein MAVS (also called IPS-1, VISA, or Cardif) on mitochondrial membranes. Activation occurs when viral RNAs (e.g., 5'-triphosphate dsRNA for RIG-I or long dsRNA for MDA5) bind, inducing conformational changes, CARD exposure, ubiquitination, and oligomerization. This triggers MAVS aggregation, recruiting TRAFs, TBK1, IKKε, and leading to phosphorylation and nuclear translocation of IRF3/IRF7 (for type I/III interferons) and NF-κB (for pro-inflammatory cytokines). The pathway distinguishes viral from host RNAs via specific RNA features and ATP hydrolysis, amplifying antiviral responses but requiring tight regulation to prevent pathology. LGP2 acts as a negative regulator.

Other names

RIG-I-like receptor (RLR) pathwayretinoic acid-inducible gene I-like receptor pathway