RNA-sensing pattern recognition receptors (RNA-sensing PRRs)

RNA-sensing pattern recognition receptors (PRRs) are a specialized group of innate immune sensors that detect viral genetic material to initiate an antiviral response [1]. This group primarily comprises endosomal Toll-like receptors (TLR3, TLR7, and TLR8) and cytosolic RIG-I-like receptors (RIG-I and MDA5) [1, 2]. TLR3 recognizes double-stranded RNA (dsRNA), while TLR7 and TLR8 detect single-stranded RNA (ssRNA) [1]. In the cytoplasm, RIG-I (DDX58) and MDA5 (IFIH1) identify various forms of viral RNA, such as 5'-triphosphorylated RNA or long dsRNA [2, 4]. Upon ligand binding, these receptors activate signaling pathways (via MAVS, TRIF, or MyD88) that culminate in the production of type I interferons (IFN-α/β) and pro-inflammatory cytokines [1, 4]. These receptors are significant therapeutic targets; agonists like imiquimod and poly(I:C) are being developed as vaccine adjuvants and cancer immunotherapies to stimulate the immune system [3]. Conversely, antagonists are being explored for treating autoimmune diseases like systemic lupus erythematosus where RNA sensing is aberrantly activated [3].

Other names

Viral RNA sensorsRNA-sensing PRRsRLRs and RNA-sensing TLRsInnate immune RNA sensors

Agonism of TLR3, TLR7, TLR8, RIG-I, or MDA5 to induce interferon production; Antagonism to inhibit inflammatory signaling.