The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy

Figure 3

Innate immunity against HCV. In HCV infected cells dsRNA replication intermediates are recognized by the cytosolic RNA sensors RIG-I and MDA5, leading to the activation of MAVS. Endosomal dsRNA is recognized by TLR3, leading to the activation of TRIF. MAVS and TRIF signal via the kinases IKK and TBK1, resulting in translocation of the transcription factors NF-κB and IRF3 to the nucleus. Here they trigger the expression of type I and type III IFNs, which are secreted and bind to their receptors in an auto- or paracrine manner. Subsequently, the JAK/STAT pathway is activated, which ultimately initiates the expression of ISGs, generating an antiviral state.