Retinoic acid-inducible gene I-like receptor (RLR) (RLR)

Retinoic acid-inducible gene I-like receptors (RLRs) are a family of cytosolic pattern recognition receptors that play a pivotal role in the innate immune system by detecting viral RNA (Loo & Gale, 2011). The family includes three members: RIG-I (DDX58), MDA5 (IFIH1), and LGP2 (DHX58), which function as RNA helicases that survey the cytoplasm for non-self RNA signatures (Yoneyama et al., 2004). RIG-I specifically recognizes short double-stranded RNA and 5'-triphosphorylated or 5'-diphosphorylated RNA, which are characteristic of viruses such as Newcastle disease virus (NDV) (Schirrmacher, 2015). Upon activation, these receptors signal through the Mitochondrial Antiviral-Signaling protein (MAVS), leading to the activation of transcription factors IRF3 and NF-kappaB, which drive the expression of Type I interferons and pro-inflammatory cytokines (Chow et al., 2018). In clinical applications, RLRs are targeted by synthetic agonists to boost antiviral responses or to enhance the immunogenicity of the tumor microenvironment in cancer therapy (Iurescia et al., 2020). Newcastle disease virus itself is utilized as an oncolytic agent, partly because its RNA triggers RIG-I-mediated apoptosis and immune activation in human tumor cells (Schirrmacher, 2015). However, therapeutic modulation of RLRs must be carefully managed to avoid excessive cytokine production or the development of autoimmune conditions like Aicardi-Goutières syndrome (Crow & Stetson, 2021).

Other names

RIG-I-like receptorRLRsDDX58RIG-IIFIH1MDA5DHX58LGP2Retinoic acid-inducible gene IMelanoma differentiation-associated protein 5Laboratory of Genetics and Physiology 2

Agonism of RIG-I-like receptors leads to the recruitment of MAVS, activation of IRF3 and NF-kappaB, and subsequent induction of Type I interferons and pro-inflammatory cytokines to stimulate antiviral and antitumor immunity.