IFN-λ: A New Class of Interferon with Distinct Functions-Implications for Hepatitis C Virus Research

Figure 2

Types I and III IFNs canonical signaling pathways. Viruses, including HCV, are recognized by pattern recognition receptor (PRR), TLR3, and/or RIG-I-like receptor, leading to the activation of kinases. This in turn results in phosphorylation of IRF3 and IRF7 and activation of NF-κB. They translocate to nucleus to form heterodimers, respectively, which can catalyze transcription of IFN-α, IFN-β, and IFN-λ genes by binding to specific DNA sequences. Then, Types I and III IFNs move out of nucleus to bind to their specific receptors on the cell membrane and trigger an overlap pathway, Jak/STAT signaling pathway. Upon binding to their cognate receptors, Type I can phosphorylate both STAT1 and STAT2 to form ISGF3 that binds to ISRE in the promoter region of ISGs to upregulate their transcription and Type III IFN also can phosphorylate STAT1 to form a homodimer GAF and induce ISGs expression with GAS in the promoter region. A myriad of ISG products is not only antiviral factors but also participation in the signaling pathway in virtue of positive/negative feedback.