The innate immune response is triggered by a variety of pathogens, including viruses, and requires rapid induction of typeⅠ?interferons (IFN), such as IFNβ and IFNα. IFN induction occurs when specific pathogen motifs bind to specific cellular receptors. In non-professional immune, virally-infected cells, IFN induction is essentially initiated after the binding of dsRNA structures to TLR3 receptors or to intracytosolic RNA helicases, such as RIG-Ⅰ/MDA5. This leads to the recruitment of specific adaptors, such as TRIF for TLR3 and the mitochondrial-associated IPS-1/VISA/MAVS/CARDIF adapter protein for the RNA helicases, and the ultimate recruitment of kinases, such as MAPKs, the canonical IKK complex and the TBK1/IKKε kinases, which activate the transcription factors ATF-2/ c-jun, NF-κB and IRF3, respectively. The coordinated action of these transcription factors leads to induction of IFN and of pro-inflammatory cytokines and to the establishment of the innate immune response. HCV can cleave both the adapters TRIF and IPS-1/VISA/MAVS/ CARDIF through the action of its NS3/4A protease. This provokes abrogation of the induction of the IFN and cytokine pathways and favours viral propagation and presumably HCV chronic infection.
