title: In vitro infection of immortalized primary hepatocytes by HCV genotype 4a and inhibition of virus replication by cyclosporin.
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 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.
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Farrash
authors.forename: Hussein H
authors.initials: HH
authors.lastname: Aly
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Hijikata
authors.forename: Hiroto
authors.initials: H
authors.lastname: Egawa
authors.forename: Kunitada
authors.initials: K
authors.lastname: Shimotohno
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D016572:Cyclosporine; C090438:(melle-4)cyclosporin