Host double-stranded RNA-induced antiviral response pathway

The host double-stranded RNA (dsRNA)-induced antiviral response pathway is a fundamental arm of the innate immune system that detects viral replication intermediates to initiate a defensive state. This pathway is activated when dsRNA, a molecular signature of many viruses, is recognized by specialized pattern recognition receptors (PRRs), including Toll-like receptor 3 (TLR3) in endosomes and RIG-I-like receptors (RIG-I and MDA5) in the cytoplasm [1, 5, 10]. Upon binding dsRNA, these receptors trigger signaling cascades through adapter proteins like MAVS and TRIF, ultimately activating transcription factors such as IRF3 and NF-kappaB to induce the expression of type I interferons (IFN-alpha/beta) and hundreds of interferon-stimulated genes (ISGs) [2, 7, 14]. Key effector proteins within this pathway, such as protein kinase R (PKR) and 2'-5'-oligoadenylate synthetase (OAS), act to halt viral protein synthesis and degrade viral RNA, respectively [1, 6, 10]. In clinical practice, this pathway is a major target for broad-spectrum antiviral therapies and cancer immunotherapies, where synthetic dsRNA mimetics like poly(I:C) and rintatolimod are used to stimulate immune responses [1, 11, 15]. However, excessive or chronic activation of these pathways can lead to severe systemic inflammation or autoimmune conditions, such as Aicardi-Goutieres syndrome, highlighting the need for precise therapeutic modulation [1, 7, 16].

Other names

dsRNA sensing pathwayInnate immune response to dsRNARLR signaling pathwayTLR3 signaling pathwayPKR/OAS pathwayType I interferon induction pathway

Agonism of pattern recognition receptors (TLR3, RIG-I, MDA5) to induce type I interferons and interferon-stimulated genes, leading to viral RNA degradation, translation inhibition, and apoptosis of infected cells.