Diverse effects of cyclosporine on hepatitis C virus strain replication

Diverse effects of cyclosporine on hepatitis C virus strain replication
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DOI:
10.1128/jvi.80.9.4510-4520.2006
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发表时间:
2006-05-01
影响因子:
5.4
通讯作者:
Shimotohno, K
Shimotohno, K
中科院分区:
医学2区
文献类型:
--
作者:
Ishii, N;Watashi, K;Shimotohno, K

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最近,已经开发了利用基因型2a JFH 1株的丙型肝炎病毒(HCV)感染性颗粒的生产系统。该菌株在细胞中具有高复制能力。环孢菌素(CsA)对HCV复制有抑制作用。在这份报告中,我们描述了CsA的抗HCV作用。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HCN菌株中,CsA治疗强烈抑制了基因型1b复制子的复制。相反,JFH 1复制对CsA及其类似物NIM 811不太敏感。JFH 1的复制不需要细胞复制辅因子亲环素B(CyPB)。CyPB刺激基因型1b复制子中的NS 5 B的RNA结合活性,但不刺激基因型2a JFH 1菌株。这些发现提供了一个洞察机制的多样性管理病毒-细胞相互作用,并在这些菌株的抗病毒药物的敏感性。
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 HCN 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.