Pattern-recognition receptor for double-stranded RNA (dsRNA PRR)

Pattern-recognition receptors (PRRs) for double-stranded RNA (dsRNA) are a critical class of innate immune sensors that detect viral replication or cellular distress [1, 4]. This group includes endosomal receptors like Toll-like receptor 3 (TLR3) and cytosolic sensors such as Retinoic acid-inducible gene I (RIG-I) and Melanoma differentiation-associated protein 5 (MDA5) [2, 3]. Upon binding to dsRNA, these receptors trigger signaling cascades involving adapter proteins like TRIF or MAVS, leading to the production of Type I interferons and pro-inflammatory cytokines [4]. In clinical applications, dsRNA PRR agonists are being developed as vaccine adjuvants and cancer immunotherapies to enhance the body's anti-tumor response by converting "cold" tumors into "hot" ones [5]. Conversely, dysregulation of these sensors is linked to autoimmune and autoinflammatory disorders, such as Aicardi-Goutières syndrome, making them potential targets for inhibitory therapies [4]. These receptors also play roles in regulating cell death and autophagy in response to viral infection [5].

Other names

dsRNA sensorsRNA-sensing pattern recognition receptorsToll-like receptor 3RIG-I-like receptorsRLRsMelanoma differentiation-associated protein 5Retinoic acid-inducible gene IProtein kinase R2-5-oligoadenylate synthetase

Agonists of dsRNA pattern-recognition receptors mimic viral infection by binding to conserved domains in sensors such as TLR3, RIG-I, or MDA5. This binding triggers the recruitment of adapter proteins (TRIF for TLR3; MAVS for RLRs), which activate downstream kinases such as TBK1 and IKK-epsilon. These kinases phosphorylate transcription factors IRF3 and IRF7, leading to their translocation to the nucleus and the subsequent induction of Type I interferons (IFN-alpha/beta) and pro-inflammatory cytokines, which stimulate both innate and adaptive immune responses [4, 5].