Fig 3.

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.