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Development of Mouse Hepatocyte Lines Permissive for Hepatitis C Virus (HCV)


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タイトル: Development of Mouse Hepatocyte Lines Permissive for Hepatitis C Virus (HCV)
著者: Aly, Hussein Hassan 著作を一覧する
Oshiumi, Hiroyuki 著作を一覧する
Shime, Hiroaki 著作を一覧する
Matsumoto, Misako 著作を一覧する
Wakita, Taka 著作を一覧する
Shimotohno, Kunitada 著作を一覧する
Seya, Tsukasa 著作を一覧する
発行日: 2011年 6月22日
出版者: Public Library of Science
誌名: PLoS One
巻: 6
号: 6
開始ページ: e21284
出版社 DOI: 10.1371/journal.pone.0021284
抄録: The lack of a suitable small animal model for the analysis of hepatitis C virus (HCV) infection has hampered elucidation of the HCV life cycle and the development of both protective and therapeutic strategies against HCV infection. Human and mouse harbor a comparable system for antiviral type I interferon (IFN) induction and amplification, which regulates viral infection and replication. Using hepatocytes from knockout (ko) mice, we determined the critical step of the IFN-inducing/ amplification pathways regulating HCV replication in mouse. The results infer that interferon-beta promoter stimulator (IPS1) or interferon A receptor (IFNAR) were a crucial barrier to HCV replication in mouse hepatocytes. Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type I interferons in response to viral infection, only IPS-1-/- cells circumvented cell death from HCV cytopathic effect and significantly improved J6JFH1 replication, suggesting IPS-1 to be a key player regulating HCV replication in mouse hepatocytes. We then established mouse hepatocyte lines lacking IPS-1 or IFNAR through immortalization with SV40T antigen. Expression of human (h)CD81 on these hepatocyte lines rendered both lines HCVcc-permissive. We also found that the chimeric J6JFH1 construct, having the structure region from J6 isolate enhanced HCV replication in mouse hepatocytes rather than the full length original JFH1 construct, a new finding that suggests the possible role of the HCV structural region in HCV replication. This is the first report on the entry and replication of HCV infectious particles in mouse hepatocytes. These mouse hepatocyte lines will facilitate establishing a mouse HCV infection model with multifarious applications.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 瀬谷 司


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