Specific inhibition of hepatitis C virus replication by cyclosporin A
Specific inhibition of hepatitis C virus replication by cyclosporin A
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DOI：
10.1016/j.bbrc.2003.11.080
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发表时间：
2004-01-02
影响因子：
3.1
通讯作者：
Watanabe, M
中科院分区：
文献类型：
--
作者：
Nakagawa, M;Sakamoto, N;Watanabe, M
根除丙型肝炎病毒（HCV）感染的困难是由于针对该病毒的治疗选择有限。最近，环孢菌素A（CsA），一种广泛使用的免疫抑制药物，已被报道对HCV感染有效[J. Gastroenterol. 38（2003）567]，尽管对其抗HCV的作用机制知之甚少。在这项研究中，我们使用HCV复制子系统研究了CsA的抗病毒作用。用表达编码荧光素酶报告基因和新霉素磷酸转移酶（Huh 7/Rep-Feo）的嵌合基因的HCV复制子转染人肝癌Huh 7细胞。用CsA处理Huh 7/Rep-Feo细胞导致HCV复制子的复制以剂量依赖性方式受到抑制，IC 50值接近0.5 μ g/ml。细胞生长速率或活力无变化，表明CsA对HCV的作用是特异性的，而不是由于细胞毒性。相反，另一种免疫抑制药物FK 506不能抑制HCV复制。CsA没有激活干扰素刺激的基因反应，表明其作用是独立的干扰素。总之，CsA在体外特异性地在临床浓度下抑制HCV复制。进一步确定其对HCV复制的作用模式可能对确定治疗HCV感染的新分子靶点很重要。(C)2003年爱思唯尔公司All rights reserved.
The difficulty in eradicating hepatitis C virus (HCV) infection is attributable to the limited treatment options against the virus. Recently, cyclosporin A (CsA), a widely used immunosuppressive drug, has been reported to be effective against HCV infection [J. Gastroenterol. 38 (2003) 567], although little is understood about the mechanism of its action against HCV. In this study, we investigated the anti-viral effects of CsA using an HCV replicon system. Human hepatoma Huh7 cells were transfected with an HCV replicon expressing a chimeric gene encoding a luciferase reporter and neomycin phosphotransferase (Huh7/Rep-Feo). Treatment of the Huh7/Rep-Feo cells with CsA resulted in suppression of the replication of the HCV replicon in a dose-dependent manner, with an IC50 of similar to0.5 mug/ml. There were no changes in the rate of cell growth or viability, suggesting that the effect of CsA against HCV is specific and not due to cytotoxicity. In contrast, FK506, another immunosuppressive drug, did not suppress HCV replication. CsA did not activate interferon-stimulated gene responses, suggesting that its action is independent of that of interferon. In conclusion, CsA inhibits HCV replication in vitro specifically at clinical concentrations. Further defining its mode of action against HCV replication potentially may be important for identifying novel molecular targets to treat HCV infection. (C) 2003 Elsevier Inc. All rights reserved.