El-Farrash Mohamed A, Aly Hussein H, Watashi Koichi, Hijikata Makoto, Egawa Hiroto, Shimotohno Kunitada
Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Egypt.
Microbiol Immunol. 2007;51(1):127-33. doi: 10.1111/j.1348-0421.2007.tb03883.x.
Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma worldwide. We previously reported that cyclosporin A (CsA) inhibits HCV-1b replication. However, its inhibition of JFH-1 (HCV-2a) was much less. Since HCV genotype clearly affects the in vitro and in vivo response to anti-viral therapy, we wished to examine the effect of CsA and its non-immunosuppressive derivative NIM811 on HCV genotype 4a replication. We first established an in vitro system supporting HCV-4a infection and replication using immortalized human hepatocytes, HuS-E7/DN24 (HuS) cells, and these cells were infected with sera obtained from Egyptian patients with chronic HCV-4a infection. HuS cells supported more robust HCV-4a replication than both HuH-7.5 and PH5CH8 cells, and HCV-4a infection and replication were completely inhibited by 3 mug/ml CsA and 0.5 mug/ml NIM811. Thus, HuS cells are a good model system supporting the infection and high-level replication of HCV-4a, and both CsA and NIM811 effectively inhibit HCV-4a replication in this system.
丙型肝炎病毒（HCV）是全球肝硬化和肝细胞癌的主要病因。我们之前报道过环孢素A（CsA）可抑制HCV-1b复制。然而，它对JFH-1（HCV-2a）的抑制作用要小得多。由于HCV基因型明显影响对抗病毒治疗的体外和体内反应，我们希望研究CsA及其非免疫抑制衍生物NIM811对HCV基因型4a复制的影响。我们首先使用永生化人肝细胞HuS-E7/DN24（HuS）细胞建立了一个支持HCV-4a感染和复制的体外系统，并用从埃及慢性HCV-4a感染患者获得的血清感染这些细胞。与HuH-7.5和PH5CH8细胞相比，HuS细胞支持更强劲的HCV-4a复制，并且3μg/ml的CsA和0.5μg/ml的NIM811可完全抑制HCV-4a感染和复制。因此，HuS细胞是支持HCV-4a感染和高水平复制的良好模型系统，并且CsA和NIM811均可有效抑制该系统中的HCV-4a复制。
