2011 Fiscal Year Final Research Report
Development of plaque assay to isolate cytopathic HCV clones
| Project/Area Number |
21590832
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OOOKA Shinya 東京医科歯科大学, 医学部・附属病院, 講師 (90361691)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Naoya 東京医科歯科大学, 大学院・医歯学総合研究科, 寄付講座教員 (10334418)
AZUMA Seishin 東京医科歯科大学, 医学部附属病院, 助教 (10376783)
WATANABE Mamoru 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
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| Project Period (FY) |
2009 – 2011
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| Keywords | HCVレプリコン / HCV-JFH1培養系 |
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| Research Abstract |
HCV-JFH1 yields subclones that develop cytopathic plaques(Sekine-Osajima Y, et al., Virology 2008 ; 371 : 71). Here, we investigated viral amino acid substitutions in cytopathic mutant HCV-JFH1 clones and their characteristics in vitro and in vivo. The mutant viruses with individual C2441S, P2938S or R2985P signature substitutions, and with all three substitutions, showed significantly higher intracellular replication efficiencies and greater cytopathic effects than the parental JFH1 in vitro. The mutant HCV-inoculated mice showed significantly higher serum HCV RNA and higher level of expression of ER stress-related proteins in early period of infection. At 8 weeks post inoculation, these signature mutations had reverted to the wild type sequences. HCV-induced cytopathogenicity is associated with the level of intracellular viral replication and is determined by certain amino acid substitutions in HCV-NS5A and NS5B regions. The cytopathic HCV clones exhibit high replication competence in vivo but may be eliminated during the early stages of infection
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[Journal Article] The inhibitory effect on hepatitis C virus infection of a triterpenoid compound, with or without interferon-alpha2011
Author(s)
Watanabe T, Sakamoto N, Nakagawa M, Kakinuma S, Itsui Y, Nishimura-Sakurai Y, Ueyama M, Funaoka Y, Kitazume A, Nitta S, Kiyohashi K, Murakawa M, Azuma S, Tsuchiya K, Oooka S, Watanabe M
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Journal Title
Antimicrob Agents Chemother
Volume: 55(6)
Pages: 2537-2545
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[Journal Article] Cell culture and in vivo analyses of cytopathic hepatitis C virus mutants2010
Author(s)
Mishima K, Sakamoto N, Sekine-Osajima Y, Nakagawa M, Itsui Y, Azuma S, Kakinuma S, Kiyohashi K, Kitazume A, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Wakita T, Watanabe M
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Journal Title
Virology
Volume: 405
Pages: 361-369
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[Journal Article] Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication2009
Author(s)
Sekine-Osajima Y, Sakamoto N, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Suda G, Mishima K, Onuki Y, Yamamoto M, Maekawa S, Enomoto N, Kanai T, Tsuchiya K, Watanabe M
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Journal Title
Hepatol Res
Volume: 39
Pages: 60-69
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