RIG-I

RIG-I is a cytosolic RNA sensor that detects viral RNA and drives innate antiviral immunity through type I interferon and inflammatory gene induction^[1]. Mechanistically, RIG-I recognizes RNA carrying a 5′-triphosphate end generated by viral polymerases, and its C-terminal regulatory domain binds this 5′-triphosphate RNA to activate downstream signaling^[2][3]. Full activation requires base-paired RNA structures together with a free 5′-triphosphate, which defines a practical ligand design principle for RIG-I activation assays^[4]. After ligand recognition, RIG-I-like receptor signaling converges on MAVS and promotes interferon-centered antiviral responses^[1][5]. In infection models, RIG-I and MDA5 show non-redundant virus recognition, and knockout studies demonstrate that both receptors remain critical for host antiviral defense^[6]. Compared with MDA5, RIG-I preferentially recognizes short 5′-triphosphate RNA ligands, whereas MDA5 recognizes long genomic RNA and replication intermediates^[7]. For experimental applications, optimized RIG-I agonist M8 induces immunogenic cell death markers in human cancer cells and activates dendritic cells, supporting its use in tumor-immune signaling studies^[8]. In HPV-associated cancer models, M8 also triggers cancer cell death and natural killer cell activation, providing a defined tool for evaluating RIG-I-driven antitumor immunity^[9].