Watashi Koichi, Shimotohno Kunitada
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Japan.
Uirusu. 2005 Jun;55(1):105-10. doi: 10.2222/jsv.55.105.
Currently, patients with hepatitis C virus (HCV) are mainly treated with interferon alone or in combination with ribavirin. However, because the virus is not eliminated from approximately one half of the patients by this treatment, alternative approaches to the treatment of HCV infection are needed. Recently, an HCV subgenomic replicon system has been established in which an HCV subgenomic replicon autonomously replicated in cultured cells. It enables us to screen for anti-HCV agents in cell culture system. Taking advantage of this system, we examined the effects of various types of compounds on the replication of HCV. Consequently, we found that a well-known immunosuppressant, cyclosporin A (CsA), had a strong suppressive activity on HCV replication, at least in cell culture system. This anti-HCV activity did not require the immunosuppressive feature of CsA. Through the investigation into the mechanism of anti-HCV effect of CsA, it was suggested that cyclophilin B, one of the cellular target molecules of CsA, played a significant role in HCV replication. Thus, searching for anti-HCV agents may lead to the elucidation of one of the mechanisms of HCV replication.
目前，丙型肝炎病毒（HCV）患者主要接受单独使用干扰素或与利巴韦林联合的治疗。然而，由于通过这种治疗大约一半的患者体内病毒并未被清除，因此需要其他治疗HCV感染的方法。最近，已建立了一种HCV亚基因组复制子系统，其中HCV亚基因组复制子在培养细胞中自主复制。这使我们能够在细胞培养系统中筛选抗HCV药物。利用该系统，我们研究了各种类型的化合物对HCV复制的影响。结果，我们发现一种著名的免疫抑制剂环孢素A（CsA）对HCV复制具有很强的抑制活性，至少在细胞培养系统中是这样。这种抗HCV活性并不需要CsA的免疫抑制特性。通过对CsA抗HCV作用机制的研究，提示环孢素A的细胞靶分子之一亲环素B在HCV复制中起重要作用。因此，寻找抗HCV药物可能会导致阐明HCV复制的机制之一。
