[The direct antiviral effect of interferon-gamma on hepatitis C virus replicon].
OBJECTIVE
To study the effects of interferon-gamma and interferon-gamma combined with interferon-alpha on HCV RNA replication and the possible mediators of interferon-gamma anti-HCV in vitro.


METHODS
An HCV replicon cell culture system was established and the cells were treated with interferon-gamma or interferon-gamma combined with interferon-alpha. HCV RNA levels in the cells were evaluated by semi-quantitative RT-PCR and real-time PCR, and the levels of NS5A protein were examined by Western blot.


RESULTS
Interferon-gamma could inhibit HCV RNA replication and NS5A protein expression effectively; The anti-HCV effects of interferon-gamma were both in time-dependent and does-dependent manners; Pretreating the cells with interferon-gamma could significantly enhance the antiviral effects of interferon-alpha; The expressions of IRF-1, 2'5'-OAS1(p46), 2'5'-OAS2(p69), ISGF3gamma and STAT1 were significantly increased after interferon-gamma treatment.


CONCLUSIONS
Interferon-gamma has a direct inhibitory effect on HCV replicon RNA replication and NS5A expression, and both are in a dose and time dependent manner; Interferon-gamma has a synergistic anti-HCV effect with interferon-alpha. IRF-1, 2'5'-OAS1(p46), 2'5'-OAS2(p69) and ISGF3gamma may mediate the anti-HCV effects of interferon-gamma.
Jia
Yin-tang
YT
Department of Infectious Diseases, First Hospital, Medical Sciences of Shanxi University, Taiyuan 030001, China.
Wei
Lai
L
Jiang
Dong
D
Cong
Xu
X
Fei
Ran
R
D000998:Antiviral Agents / Q000494:pharmacology*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology; D008297:Male; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D012093:Replicon / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D007371:Interferon-gamma