Antiviral action of interferon-alpha against hepatitis C virus replicon and its modulation by interferon-gamma and interleukin-8.
OBJECTIVE
Interferon-alpha (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-alpha 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-alpha 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.


CONCLUSIONS
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.
Jia
Yintang
Y
Hepatology Institute, Peking University People's Hospital, Beijing, China.
Wei
Lai
L
Jiang
Dong
D
Wang
Jianghua
J
Cong
Xu
X
Fei
Ran
R
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects; D012093:Replicon / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D016209:Interleukin-8; D012367:RNA, Viral; D007371:Interferon-gamma