Interferon (IFN) in combination with ribavirin has been the standard of care (SOC) for chronic hepatitis C for the past few decades. Although the current SOC lacks the desired efficacy, and 4 new direct-acting antiviral agents have been recently approved, interferons are still likely to remain the cornerstone of therapy for some time. Moreover, as an important cytokine system of innate immunity, host interferon signaling provides a powerful antiviral response. Nevertheless, the mechanisms by which HCV infection controls interferon production, and how interferons, in turn, trigger anti-HCV activities as well as control the outcome of HCV infection remain to be clarified. In this report, we review current progress in understanding the mechanisms of IFN against HCV, and also summarize the knowledge of induction of interferon signaling by HCV infection.
Keywords: Antiviral agent; CHC, chronic hepatitis C; DCs, dendritic cells; DNAM1, DNAX accessory molecule-1; E2, envelop 2; GAS, IFN-γ-activated site; GWAS, genome-wide association studies; Hepatitis C virus; IFN, interferon; IFN-α, interferon-α; IFNAR1, interferon-alpha receptor 1; IFNAR2, interferon-alpha receptor 2; IFNGR1, interferon gamma receptor 1; IFNGR2, interferon gamma receptor 2; IFNL4, IFN-lambda 4; IL-10R2, interleukin-10 receptor 2; IL-29, interleukin-29; IRF-3, interferon regulatory factor 3; IRGs, IFN regulatory genes; ISG15, interferon-stimulated gene 15; ISGF3, IFN-stimulated gene factor 3; ISGs, IFN-stimulated genes; ISREs, IFN-stimulated response elements; Interferon; JAKs, Janus activated kinases; MAVS, mitochondrial antiviral signaling protein; MDA-5, melanoma differentiation-associated gene-5; MHC, major histocompatibility complex; Molecular mechanism; NKCs, natural killer cells; NKTCs, natural killer T cells; OAS, 2′-5′-oligoadenylate synthetase; PAMPs, pathogen-associated molecular patterns; PBMCs, peripheral blood mononuclear cells; PKR, protein kinase R; PRRs, pattern recognition receptors; RIG-I, retinoic acid-inducible gene-I; RLRs, RIG-I-like receptors; RdRp, RNA dependent RNA polymerase; SNPs, single-nucleotide polymorphisms; SOC, standard of care; STAT1, signal transducer and activator of transcription 1; STAT2, signal transducer and activator of transcription 2; SVR, sustained virological response; TH1, T-helper-1; TH2, T-helper-2; TLRs, Toll-like receptors; TYK2, tyrosine kinase 2; USP18, ubiquitin specific peptidase 18; dsRNA, double-stranded RNA; pDC, plasmacytoid dendritic cell.