1. Key airway signaling pathways induced by respiratory viruses.
Key airway signaling pathways induced by respiratory viruses. TLR3 is expressed in intracellular endosomes and recognizes viral ssRNAs, such as those of rhinovirus, RSV, and influenza virus. TLR3 activates IRF-3 via the Toll/IL-1 receptor domain-containing adaptor (TRIF), resulting in IFN-β and IFN-λ1 production. TLR3 also activates IRF-7 and NF-κB through MyD88 activation. Activation of NF-κB and IRF-7 leads to the production of proinflammatory cytokines and the production of IFN-α, -λ1, and -λ2/3, respectively. Other endosomal TLRs (TLR7/8 and TLR9) detect ssRNAs and dsRNAs, such as those of influenza virus and adenovirus. Both TLR7/8 and TLR9 signal through a MyD88-dependent pathway, leading to the activation of NF-κB and IRF-7. TLR4 is expressed on the cell surface and responds to the RSV fusion protein. TLR4 signals through MyD88 to activate NF-κB and through TRIF to activate IRF-7. The two RNA helicases RIG-I and MDA5 detect viral replication products in the cytosol to activate IRF-3 via the adaptor protein IPS-1/MAVS/VISA/Cardif.
Marjolaine Vareille et al. Clin. Microbiol. Rev. 2011; doi: /CMR