Melanoma differentiation-associated protein 5 (MDA5) and Retinoic acid-inducible gene I (RIG-I) (MDA5 (for IFIH1 gene), RIG-I (for DDX58 gene))

MDA5 and RIG-I are cytosolic RNA sensors belonging to the RIG-I-like receptor (RLR) family. They detect distinct viral RNA signatures: RIG-I recognizes short double-stranded RNA with 5′-triphosphate ends, while MDA5 detects long double-stranded RNA molecules, including those from picornaviruses and other RNA viruses[1][2][3][4][5][7]. Their activation triggers production of type I interferons and other antiviral cytokines by recruiting adaptor proteins (e.g., MAVS), initiating a signaling cascade essential for effective antiviral defense[7]. Deregulation or dysfunction of these receptors can contribute to chronic inflammation, autoimmunity, and sometimes pathogenic reactions during infection or cancer[7]. Recent interest includes developing modulators of these receptors for cancer immunotherapy, antiviral agents, and treatments for autoimmune disorders.

Other names

IFIH1Interferon-induced helicase C domain-containing protein 1DDX58DEAD box protein 58Retinoic acid-inducible gene I

Agonists bind to the RNA sensor domains, mimicking viral RNA and activating downstream interferon pathways\nPotential antagonists block RNA recognition or downstream signaling to dampen interferon responses.