Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates the Antiviral Action of Interferon
Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates the Antiviral Action of Interferon
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DOI：
10.1086/593216
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发表时间：
2008-12-15
影响因子：
6.4
通讯作者：
Beard, Michael R.
中科院分区：
文献类型：
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作者：
McCartney, Erin M.;Semendric, Ljiljana;Beard, Michael R.
丙型肝炎病毒（HCV）与酒精代谢之间的相互作用尚不清楚。为了确定酒精代谢对HCV复制和干扰素（IFN）的抗病毒作用的影响，用乙醇和IFN-α处理携带HCV复制并通过引入细胞色素P450 2 E1（Cyp 2 e1）的表达代谢乙醇的Huh-7细胞。用乙醇（0-100 mmol/L）处理这些细胞显著增加HCV复制。这种作用依赖于Cyp 2 e1的表达和酒精代谢的氧化应激（OS），因为抗氧化剂N-乙酰半胱氨酸阻断了这种作用。此外，IFN-α的抗HCV作用在乙醇代谢的存在下减弱，最有可能是通过减弱Stat 1酪氨酸-701磷酸化。这些体外结果模拟了临床上经常注意到的情况，进一步解剖该模型系统将有助于我们理解HCV和酒精代谢之间的相互作用。
The interactions between hepatitis C virus (HCV) and alcohol metabolism are not well understood. To determine the effect that alcohol metabolism has on HCV replication and the antiviral action of interferon (IFN), Huh-7 cells that harbor HCV replication and metabolize ethanol via the introduced expression of cytochrome P450 2E1 (Cyp2e1) were treated with ethanol and IFN-alpha. Treatment of these cells with ethanol (0-100 mmol/L) significantly increased HCV replication. This effect was dependent on Cyp2e1 expression and alcohol-metabolized oxidative stress (OS), because the antioxidant N-acetylcysteine blocked this effect. Furthermore, the anti-HCV action of IFN-alpha was attenuated in the presence of ethanol metabolism, most likely via attenuation of Stat1 tyrosine-701 phosphorylation. These in vitro results mimic what is often noted clinically, and further dissection of this model system will aid in our understanding of interactions between HCV and alcohol metabolism.