环孢素对丙型肝炎病毒株复制的多种作用。
Diverse effects of cyclosporine on hepatitis C virus strain replication.
作者信息
Ishii Naoto, Watashi Koichi, Hishiki Takayuki, Goto Kaku, Inoue Daisuke, Hijikata Makoto, Wakita Takaji, Kato Nobuyuki, Shimotohno Kunitada
机构信息
Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
出版信息
J Virol. 2006 May;80(9):4510-20. doi: 10.1128/JVI.80.9.4510-4520.2006.
Recently, a production system for infectious particles of hepatitis C virus (HCV) utilizing the genotype 2a JFH1 strain has been developed. This strain has a high capacity for replication in the cells. Cyclosporine (CsA) has a suppressive effect on HCV replication. In this report, we characterize the anti-HCV effect of CsA. We observe that the presence of viral structural proteins does not influence the anti-HCV activity of CsA. Among HCV strains, the replication of genotype 1b replicons was strongly suppressed by treatment with CsA. In contrast, JFH1 replication was less sensitive to CsA and its analog, NIM811. Replication of JFH1 did not require the cellular replication cofactor, cyclophilin B (CyPB). CyPB stimulated the RNA binding activity of NS5B in the genotype 1b replicon but not the genotype 2a JFH1 strain. These findings provide an insight into the mechanisms of diversity governing virus-cell interactions and in the sensitivity of these strains to antiviral agents.
最近，一种利用丙型肝炎病毒（HCV）2a基因型JFH1株生产感染性病毒颗粒的系统已被开发出来。该毒株在细胞中具有高复制能力。环孢素（CsA）对HCV复制有抑制作用。在本报告中，我们对CsA的抗HCV作用进行了表征。我们观察到病毒结构蛋白的存在并不影响CsA的抗HCV活性。在HCV毒株中，1b基因型复制子的复制受到CsA处理的强烈抑制。相比之下，JFH1的复制对CsA及其类似物NIM811不太敏感。JFH1的复制不需要细胞复制辅助因子亲环素B（CyPB）。CyPB刺激了1b基因型复制子中NS5B的RNA结合活性，但对2a基因型JFH1毒株没有刺激作用。这些发现为控制病毒-细胞相互作用的多样性机制以及这些毒株对抗病毒药物的敏感性提供了见解。
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