ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>