In Vitro Infection of Immortalized Primary Hepatocytes by HCV Genotype 4a and Inhibition of Virus Replication by Cyclosporin

Authors

  • Mohamed A. El-Farrash,

    1. Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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  • Hussein H. Aly,

    1. Graduate School of Medicine, Department of Transplant Surgery, Kyoto University Hospital, Kyoto, Kyoto, Japan
    2. Laboratory for Human Tumor Viruses, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan
    3. Hepatology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
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  • Koichi Watashi,

    1. Laboratory for Human Tumor Viruses, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan
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  • Makoto Hijikata,

    1. Laboratory for Human Tumor Viruses, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan
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  • Hiroto Egawa,

    1. Graduate School of Medicine, Department of Transplant Surgery, Kyoto University Hospital, Kyoto, Kyoto, Japan
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  • Kunitada Shimotohno

    Corresponding author
    1. Laboratory for Human Tumor Viruses, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, Japan
    • Address correspondence to Dr. Kunitada Shimotohno, The Institute for Virus Research, Kyoto University, 53 Kawaharacho Shogoin, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan. Fax: + 81-75-751-3998. E-mail: kshimoto@virus.kyoto-u.ac.jp

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Abstract

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 μg/ml CsA and 0.5 μg/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.

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