1. Signal transduction pathways and activation of the innate immune response.
Signal transduction pathways and activation of the innate immune response. In the endosome, viral dsRNA and ssRNA are recognized by TLR3 and TLR7/8, respectively. An interaction with TLR3 triggers the upregulation of the pattern recognition receptors (retinoic acid-inducible gene 1 [RIG-1] and melanoma differentiation-associated protein 5 [MDA-5]) (RNA helicases) in the intracellular compartment. RIG-1 and MDA-5 also recognize newly synthesized viral dsRNA and ssRNA in the cytoplasm. RIG-1 and MDA-5 stimulate HRV-induced IFN gene expression as well as the increased production of T cell and neutrophil cytokines, including regulated, normal T cell expressed, and secreted (RANTES); IFN-γ-induced protein 10 (IP-10); IL-8; and epithelial cell-derived neutrophil-activating peptide 78 (ENA78). An interaction with TLR7/8 triggers IFN-β and IFN-γ production and activates the NF-κβ pathway. HRV also interacts with TLR2 on the cell surface to initiate a proinflammatory cytokine response via a MyD88-dependent pathway (38, 39). LDLR, low-density-lipoprotein receptor; ICAM-1, intercellular adhesion molecule 1; TIRAP, Toll–interleukin-1 receptor (TIR) domain containing adaptor protein; PMNs, polymorphonuclear leukocytes.
Samantha E. Jacobs et al. Clin. Microbiol. Rev. 2013; doi: /CMR