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. Author manuscript; available in PMC: 2014 Jan 1.
Published in final edited form as: Semin Immunopathol. 2012 Aug 7;35(1):53–72. doi: 10.1007/s00281-012-0332-x

Figure 2. Innate intracellular signaling pathways that sense RNA virus infections and lead to expression of type I and III IFNs, cytokines and chemokines.

Figure 2

Viral dsRNAs and 5′-triphosphate-bearing, poly-U rich viral RNAs are recognized by the RLRs (RIG-I, MDA5 and LGP2) that are constitutively expressed in the cytoplasm and that initiate MAVS-dependent signaling leading to activation of IRF3/7 and NF-κB, and ultimately, synthesis of type I and III IFNs and inflammatory cytokines/chemokines. Viral dsRNAs can also be sensed by TLR3 in late endosomes and trigger a TRIF-dependent pathway activating innate immune responses. Both the RIG-I and TLR3 pathways are capable of sensing HCV infection in hepatocytes. Viral ssRNAs can be sensed by TLR7 or TLR8 in endosomes and activate MyD88-dependent innate immune responses. TLR7 operates exclusively in pDCs and mainly results in IRF7 activation and subsequent induction of IFN-α and IFN-λs, while TLR8 operates in mDCs and mainly leads to expression of NF-κB-dependent cytokines. pDCs use the TLR7 pathway to sense co-cultured HCV-infected hepatocytes, resulting in IFN-α production.