Development of Mouse Hepatocyte Lines Permissive for Hepatitis C Virus (HCV)
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概要
- 論文の詳細を見る
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.
- 2011-06-22
著者
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Matsumoto Misako
北海道大学 医学研究科免疫学
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Matsumoto M
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Seya Tsukasa
大阪府立成人病センター研究所 免疫学部門
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Seya Tsukasa
北海道大学 医学研究科免疫学
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Seya Tsukasa
Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases:probrain
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松本 美佐子
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Seto Toshiyuki
Daparment Of Virology
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Matsumoto Masanori
Laboratory Of Immunodynamics Department Of Microbiology And Immunology Osaka University Graduate Sch
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