Antiviral action of interferon-α against hepatitis C virus replicon and its modulation by interferon-γ and interleukin-8

作者:Jia, Yintang; Wei, Lai*; Jiang, Dong; Wang, Jianghua; Cong, Xu; Fei, Ran
来源:Journal of Gastroenterology and Hepatology, 2007, 22(8): 1278-1285.
DOI:10.1111/j.1440-1746.2007.04957.x

摘要

Background and Aim: Interferon-a (IFN-alpha) based therapy is the main treatment used to control hepatitis C virus (HCV) infection. The aim of this study was to understand the mechanisms of IFN-alpha inhibition of HCV replication and the resistance of HCV to IFN-alpha therapy, and improve the efficiency of HCV treatment. @@@ Methods: The inhibitory effects of IFN-a on a HCV replicon system were examined and the potential regulatory effects of interferon-gamma (IFN-gamma) and interleukin-8 (IL-8) on the antiviral actions of IFN-a were also investigated in this report. @@@ Results: The results showed that IFN-alpha can effectively inhibit the replication of HCV replicon. Pretreatment of HCV replicon cells with IFN-gamma could significantly potentiate the inhibitory effects of IFN-alpha on the HCV replicon. Direct addition of IL-8 to the culture medium of HCV replicon cells could partially rescue the HCV replicon from the inhibition of IFN-alpha, which may be the result of IL-8 down-regulation of interferon-stimulated genes. @@@ Conclusion: Our study demonstrated that IFN-gamma has synergistic antiviral effects with IFN-alpha; whereas IL-8 can attenuate the anti-HCV actions of IFN-alpha and is associated with HCV resistance to interferon-alpha therapy.