Long viral double-stranded RNA (dsRNA)

Long viral double-stranded RNA (dsRNA) is a critical molecular signature produced during the replication cycle of most viruses, including both RNA and DNA viruses. It is recognized by the host cell as a danger signal or Pathogen-Associated Molecular Pattern (PAMP) because long dsRNA is typically absent in healthy eukaryotic cells (Alexopoulou et al., 2001, Nature). The detection of dsRNA is mediated by several Pattern Recognition Receptors (PRRs), most notably Toll-like receptor 3 (TLR3) in the endosomal compartment and Melanoma Differentiation-Associated protein 5 (MDA5) and Protein Kinase R (PKR) in the cytoplasm (Kato et al., 2006, Nature; Garcia et al., 2006, Microbiol Mol Biol Rev). Upon binding, these sensors initiate signaling cascades that culminate in the induction of Type I interferons (IFN-α and IFN-β) and other pro-inflammatory cytokines, which are essential for establishing an antiviral state and bridging innate and adaptive immunity. Therapeutically, synthetic analogs of long dsRNA, such as Rintatolimod and Poly-ICLC, are developed as potent immunotherapeutic agents and vaccine adjuvants to treat viral infections and malignancies (Jasani et al., 2009, Vaccine). However, the clinical application of dsRNA-based therapies is often limited by the risk of systemic inflammatory toxicity and the need for precise delivery to avoid off-target effects (Stark et al., 2020, Frontiers in Immunology).

Other names

Double-stranded RNAViral dsRNALong dsRNAvdsRNAPolyadenylic-polyuridylic acid (Poly(A:U))Polyinosinic-polycytidylic acid (Poly(I:C))

Activation of Pattern Recognition Receptors (PRRs) such as Toll-like receptor 3 (TLR3), Melanoma Differentiation-Associated protein 5 (MDA5), and Protein Kinase R (PKR) to induce Type I interferon and pro-inflammatory cytokine production.