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2008 Fiscal Year Final Research Report

Analysis of factors involved in viral replication efficiency and search for novel anti -virals using HCV culture systems.

Research Project

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Project/Area Number 18390225
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

WAKITA Takaji  National Institute of Infectious Diseases, ウイルス第二部, 部長 (40280789)

Co-Investigator(Kenkyū-buntansha) DATE Tomoko  国立感染症研究所, ウイルス第二部, 研究員 (40392360)
MORIKAWA Kenichi  国立感染症研究所, ウイルス第二部, 協力研究員 (60384377)
AIZAKI Hideki  国立感染症研究所, ウイルス第二部, 主任研究官 (00333360)
MURAKAMI Kyoko  国立感染症研究所, ウイルス第二部, 主任研究官 (30399456)
ISHII Koji  国立感染症研究所, ウイルス第二部, 主任研究官 (40280763)
SUZUKI Ryosuke  国立感染症研究所, ウイルス第二部, 主任研究官 (50342902)
Project Period (FY) 2006 – 2008
KeywordsHCV / ウイルス / 感染実験 / ウイルス複製 / インターフェロン
Research Abstract

C型肝炎ウイルス(HCV)感染症は持続感染化して慢性肝炎から肝硬変、肝臓癌に至る疾患を引き起こす。HCVはプラス鎖RNA をゲノムとするウイルスであり、ウイルスゲノムの変異が多い。ウイルスゲノムの変異がウイルスの持続感染化に関与すると考えられているがその詳細は不明である。HCVの研究はウイルス培養系が存在せず、感染性ウイルスを用いた研究ができなかった。我々が分離したJFH-1株は培養細胞で感染および増殖複製が世界で初めて可能であることを報告した。本研究では、HCVがどのような機構で感染増殖効率を規定しているかを解析し、ウイルス複製増殖に関与する、ウイルス側および宿主側因子を同定した。この研究により、新たな抗ウイルス戦略の標的を探索した。

  • Research Products

    (64 results)

All 2009 2008 2007 2006

All Journal Article (39 results) Presentation (23 results) Book (2 results)

  • [Journal Article] Involvement of creatine kinase B in hepatitis C virus genome replication through interaction with the viral NS4A protein.2009

    • Author(s)
      Hara H, 他10名 Wakita T, Suzuki T.
    • Journal Title

      J Virol. 83(10)

      Pages: 5137-47

  • [Journal Article] Hepatitis C Virus Infection of T Cells Inhibits Proliferation and Enhances Fas-Mediated Apoptosis by Down-Regulating the Expression of CD44 Splicing Variant 6.2009

    • Author(s)
      Kondo Y, 他4名Wakita T, Shimosegawa T, Lai MM.
    • Journal Title

      J Infect Dis. 199(5)

      Pages: 726-736

  • [Journal Article] Virus RNA Replication through Modulation of the Glutathione Redox System and Oxidative Stress.2009

    • Author(s)
      Kuroki M, 他3名 Wakita T, Kato N.
    • Journal Title

      J Virol. 83(5)

      Pages: 2338-48

  • [Journal Article] Proteasomal Turnover of Hepatitis C Virus Core Protein Is Regulated by Two Distinct Mechanisms: a Ubiquitin-Dependent Mechanism and a Ubiquitin-Independent but PA28{gamma}-Dependent Mechanism.2009

    • Author(s)
      Suzuki R, 他5名Wakita T, Miyamura T, Matsuura Y, Suzuki T.
    • Journal Title

      J Virol. 83(5)

      Pages: 2389-92

  • [Journal Article] Cellular vimentin content regulates the protein level of hepatitis C virus core protein and the hepatitis C virus production in cultured cells.2009

    • Author(s)
      Nitahara-Kasahara Y, 他5名 Wakita T, Hanada K, Miyamura T, Nishijima M.
    • Journal Title

      Virol. 383(2)

      Pages: 319-27

  • [Journal Article] Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity.2008

    • Author(s)
      Sekine-Osajima Y, 他9名Wakita T, Enomoto N, Watanabe M.
    • Journal Title

      Virol. 371(1)

      Pages: 71-85

  • [Journal Article] Characterization of infectious hepatitis C virus from liver -derived cell lines.2008

    • Author(s)
      Akazawa D, 他10名 Wakita T.
    • Journal Title

      BBRC. 377(3)

      Pages: 747-51

  • [Journal Article] Hepatitis C virus infection sensitizes human hepatocytes to TRAIL -induced apoptosis in a caspase 9-dependent manner.2008

    • Author(s)
      Lan L, 他7名 Wakita T, 他5名
    • Journal Title

      J Immunol. 181(7)

      Pages: 4926-35

  • [Journal Article] Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation.2008

    • Author(s)
      Kato T, 他6名 Wakita T, Krawczynski K, Liang TJ.
    • Journal Title

      Hepatology. 48(3)

      Pages: 732-40

  • [Journal Article] The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication.2008

    • Author(s)
      Ariumi Y, 他4名 Wakita T, Kato N.
    • Journal Title

      J Virol. 82(19)

      Pages: 9639-46

  • [Journal Article] Virological characterization of the hepatitis C virus JFH -1 strain in lymphocytic cell lines.2008

    • Author(s)
      Murakami K, 他5名 Wakita T, Shoji I.
    • Journal Title

      J Gen Virol. 89(7)

      Pages: 1587-92

  • [Journal Article] Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles.2008

    • Author(s)
      Masaki T, 他8名 Wakita T, Suzuki T.
    • Journal Title

      J Virol. 82(16)

      Pages: 7964-76

  • [Journal Article] Intragenotypic JFH1 based recombinant hepatitis C virus produces high levels of infectious particles but causes increased cell death.2008

    • Author(s)
      Mateu G, Donis RO, Wakita T, Bukh J, Grakoui A.
    • Journal Title

      Virol. 376(2)

      Pages: 397-407

  • [Journal Article] Trans-encapsidation of hepatitis C virus subgenomic replicon RNA with viral structure proteins.2008

    • Author(s)
      Ishii K, 他8名 Wakita T, Suzuki T.
    • Journal Title

      BBRC. 371(3)

      Pages: 446-50

  • [Journal Article] Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon.2007

    • Author(s)
      Hiraga N, 他15名 Wakita T, Chayama K.
    • Journal Title

      FEBS Lett. 581(10)

      Pages: 1983-7

  • [Journal Article] CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection.2007

    • Author(s)
      Akazawa D, 他8名Wakita T.
    • Journal Title

      J Virol. 81(10)

      Pages: 5036-45

  • [Journal Article] Production of infectious hepatitis C virus of various genotypes in cell cultures.2007

    • Author(s)
      Kato T, 他5名Wakita T, Liang TJ.
    • Journal Title

      J Virol. 81(9)

      Pages: 4405-11

  • [Journal Article] The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles.2007

    • Author(s)
      Morikawa K, 他7名Wakita T.
    • Journal Title

      J Med Virol. 79(6)

      Pages: 714-23

  • [Journal Article] Borras-Cuesta F, Lasarte JJ, Prieto J. Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection.2007

    • Author(s)
      Larrea E, 他9名Wakita T
    • Journal Title

      J Virol. 81(7)

      Pages: 3662-6

  • [Journal Article] An infectious and selectable full-length replicon system with hepatitis C virus JFH-1 strain.2007

    • Author(s)
      Date T, 他8名Wakita T.
    • Journal Title

      Hepatol Res. 37(6)

      Pages: 433-43

  • [Journal Article] E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein.2007

    • Author(s)
      Shirakura M, 他12名Wakita T, Suzuki T, Howley PM, Miyamura T, Shoji I.
    • Journal Title

      J Virol. 81(3)

      Pages: 1174-85

  • [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response.2007

    • Author(s)
      Tasaka M, 他9名Wakita T, Maekawa S, Enomoto N, Watanabe M.
    • Journal Title

      J Gen Virol. 88

      Pages: 3323-33

  • [Journal Article] Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81.2007

    • Author(s)
      Zeisel MB, 他5 名Wakita T, 他11名
    • Journal Title

      Hepatology. 46(6)

      Pages: 1722-1731

  • [Journal Article] DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication.2007

    • Author(s)
      Ariumi Y, 他4名Wakita T, Kato N.
    • Journal Title

      J Virol. 81(24)

      Pages: 13922-6

  • [Journal Article] The lipid droplet is an important organelle for hepatitis C virus production.2007

    • Author(s)
      Miyanari Y, 他6名Wakita T, Hijikata M, Shimotohno K.
    • Journal Title

      Nat Cell Biol. 9(9)

      Pages: 1089-97

  • [Journal Article] Robust production of infectious viral particles in Huh-7 cells by introducing mutations in hepatitis C virus structural proteins.2007

    • Author(s)
      Delgrange D, 他5名Wakita T, Duverlie G, Wychowski C.
    • Journal Title

      J Gen Virol. 88(9)

      Pages: 2495-503

  • [Journal Article] Monitoring the antiviral effect of alpha interferon on individual cells.2007

    • Author(s)
      Kim CS, Jung JH, Wakita T, 他2名
    • Journal Title

      J Virol. 81(16)

      Pages: 8814-20

  • [Journal Article] The NS3 helicase and NS5B-to-3'X regions are important for efficient hepatitis C virus strain JFH-1 replication in Huh7 cells.2007

    • Author(s)
      Murayama A, 他9名Wakita T.
    • Journal Title

      J Virol. 81(15)

      Pages: 8030-40

  • [Journal Article] Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon.2007

    • Author(s)
      Hiraga N, 他15名Wakita T, Chayama K.
    • Journal Title

      FEBS Lett. 581(10)

      Pages: 1983-7

  • [Journal Article] Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice.2007

    • Author(s)
      Kimura T, 他16名 Wakita T, Okamoto T, Matsuura Y, Chayama K.
    • Journal Title

      J Gen Virol. 89(9)

      Pages: 2108-13

  • [Journal Article] Cell culture and infection system for hepatitis C virus.2006

    • Author(s)
      Kato T, 他4名 Wakita T.
    • Journal Title

      Nat Protoc. 1(5)

      Pages: 2334-9

  • [Journal Article] Replication of a hepatitis C virus replicon clone in mouse cells.2006

    • Author(s)
      SL Uprichard, J Chung, FV Chisari, T Wakita.
    • Journal Title

      Virology J. 3

      Pages: 89

  • [Journal Article] Regulation of CXCL-8 (Interleukin 8) Induction by dsRNA Signaling Pathways During Hepatitis C Virus Infection.2006

    • Author(s)
      Wagoner J, 他6名Wakita T, Gale M Jr, Polyak SJ.
    • Journal Title

      J Virol. 81(1)

      Pages: 309-18

  • [Journal Article] Hepatitis C virus entry depends on Clathrin-Mediated Endocytosis.2006

    • Author(s)
      E Blanchard, S Belouzard, L Goueslain, T Wakita, 他3名
    • Journal Title

      J Virol, 80(14)

      Pages: 6964-72

  • [Journal Article] Generation of infectious hepatitis C virus in immortalized human hepatocytes.2006

    • Author(s)
      T Kanda, A Basu, R Steele, T Wakita, 他3名
    • Journal Title

      J Virol. 80(9)

      Pages: 4633-9

  • [Journal Article] Characterization of the replication sensitivity to cyclosporin A among strains of hepatitis C virus.2006

    • Author(s)
      N Ishii, 他5名 T Wakita, N Kato, K Shimotohno.
    • Journal Title

      J Virol, 80(9)

      Pages: 4510-20

  • [Journal Article] A novel virus culture system for hepatitis C virus.2006

    • Author(s)
      Kato T, Date T, Miyamoto M, Wakita T.
    • Journal Title

      Future Virology 1

      Pages: 519-525

  • [Journal Article] Subcellular localization of hepatitis C virus structural proteins in a cell culture system that efficiently replicates the virus.2006

    • Author(s)
      Y Rouille, 他9名T Wakita, C Wychowski, J Dubuisson.
    • Journal Title

      J Virol. 80(6)

      Pages: 2832-41

  • [Journal Article] Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells.2006

    • Author(s)
      Yi M, Villanueva RA, Thomas DL, Wakita T, Lemon SM.
    • Journal Title

      PNAS. 103(7)

      Pages: 2310-5

  • [Presentation] C型肝炎ウイルスのウイルス培養とワクチン開発2008

    • Author(s)
      脇田隆字
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      20081028-30
  • [Presentation] ATM DNA損傷センサーはC型肝炎ウイルスのRNA複製に必要である2008

    • Author(s)
      有海康雄、他4名、脇田隆字、加藤宜之
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      20081028-30
  • [Presentation] creatine kinase BはC型肝炎ウイルスNS4Aとの相互作用によりウイルスゲノム複製複合体へ運ばれエネルギー供給に働く2008

    • Author(s)
      原弘道、相崎英樹、他5名、脇田隆字、鈴木哲朗
    • Organizer
      日本ウイルス学会第56回学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      20081026-28
  • [Presentation] HCV粒子形成におけるNS5A蛋白の役割2008

    • Author(s)
      政木隆博、鈴木亮介、村上恭子、相崎英樹、石井孝司、村山麻子、伊達朋子、松浦善治、宮村達男、脇田隆字、鈴木哲朗
    • Organizer
      日本ウイルス学会第56回学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      20081026-28
  • [Presentation] In silicoscreeningによるHCV NS3プロテアーゼ阻害化合物の検索2008

    • Author(s)
      山下篤哉、他6名、脇田隆字、梅山秀明、横山茂之、榎本信幸、伊藤正彦
    • Organizer
      日本ウイルス学会第56回学術集会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      20081026-28
  • [Presentation] 培養細胞で作製した感染性C型肝炎ウイルス粒子の免疫原性の解析およびワクチン応用への可能性2008

    • Author(s)
      森川賢一、脇田隆字
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      愛媛県県民文化会館
    • Year and Date
      20080605-06
  • [Presentation] HCV JFH-1株のチンパンジーへの感染実験 : in vivo適応変異の機能的解析2008

    • Author(s)
      加藤孝宣、三代俊治、脇田隆字
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      愛媛県県民文化会館
    • Year and Date
      20080605-06
  • [Presentation] HCV culture system and antiviral development2008

    • Author(s)
      T Wakita.
    • Organizer
      21^<st> International Conference on Antiviral Research (ICAR)
    • Place of Presentation
      Montreal, Quebec, Canada
    • Year and Date
      20080413-17
  • [Presentation] C型肝炎ウイルス研究の最先端2008

    • Author(s)
      脇田隆字
    • Organizer
      第12回日本肝臓学会大会
    • Place of Presentation
      グランドプリンスホテル新高輪
    • Year and Date
      2008-10-01
  • [Presentation] Hepatitis C virus replication and virus particle formation, Symposium: Emerging Viruses and the Control of Viruses2008

    • Author(s)
      T Wakita
    • Organizer
      XIVth International Congress of Virology, IUMS
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2008-08-15
  • [Presentation] C型肝炎ウイルス研究の進展 : ウイルス増殖からワクチン開発へ2008

    • Author(s)
      脇田隆字
    • Organizer
      第134回日本医学会シンポジウム「感染症をめぐる最近の話題」
    • Place of Presentation
      日本医師会館
    • Year and Date
      2008-07-17
  • [Presentation] C型肝炎ウイルスに対するワクチン開発、2007

    • Author(s)
      脇田隆字
    • Organizer
      第11回日本ワクチン学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20071208-09
  • [Presentation] 遺伝子型2a/2b間でのキメラウイルスの作製および性状解析2007

    • Author(s)
      伊達朋子、村山麻子、赤澤大輔、森川賢一、石井孝司、野本明男、鈴木哲朗、脇田隆字
    • Organizer
      日本ウイルス学会第55回学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      20071021-23
  • [Presentation] HCV JFH-1株の複製および感染性ウイルス粒子形成に重要な領域の解析2007

    • Author(s)
      村山麻子、伊達朋子、赤澤大輔、森川賢一、石井孝司、鈴木哲朗、脇田隆字
    • Organizer
      日本ウイルス学会第55回学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      20071021-23
  • [Presentation] HCV JFH-1株のin vivoでの病原性の検討2007

    • Author(s)
      加藤孝宣、脇田隆字
    • Organizer
      日本ウイルス学会第55回学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      20071021-23
  • [Presentation] 肝細胞株における感染性HCV粒子の作製と性状解析2007

    • Author(s)
      赤澤大輔、伊達朋子、森川賢一、他5名、脇田隆字
    • Organizer
      日本ウイルス学会第55回学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      20071021-23
  • [Presentation] The important regions for RNA replication and infectious virus particle formation of JFH-12007

    • Author(s)
      Murayama A, Date T, Morikawa K, Akazawa D, Ishii K, Wakita T
    • Organizer
      14th International Meeting on Hepatitis C and Related Viruses.
    • Place of Presentation
      Glasgow, Scotland, UK
    • Year and Date
      20070909-13
  • [Presentation] Characterization of infectious HCV particles produced from various liver-derived cell lines2007

    • Author(s)
      Akazawa D, Takahashi H, Omi N, Date T, Morikawa K, Murayama A, Nakamura N, Mochizuki H, Wakita T
    • Organizer
      14th International Meeting on Hepatitis C and Related Viruses.
    • Place of Presentation
      Glasgow, Scotland, UK
    • Year and Date
      20070909-13
  • [Presentation] Analysis of NS5A region for hepatitis C virus particle production2007

    • Author(s)
      Masaki T, Suzuki R, Miyamura T, Wakita T, Suzuki T
    • Organizer
      14th International Meeting on Hepatitis C and Related Viruses.
    • Place of Presentation
      Glasgow, Scotland, UK
    • Year and Date
      20070909-13
  • [Presentation] Critical roles of virion-associated cholesterol and sphingolipids in the viral infectivity2007

    • Author(s)
      T Wakita, H Aizaki
    • Organizer
      The 7^<th> Awaji International Forum on Infection and Immunity
    • Place of Presentation
      The Hyogo Prefecture Awaji Yumebutai International Conference Center
    • Year and Date
      20070901-05
  • [Presentation] 脂質のC型肝炎ウイルス感染、粒子形成における役割2007

    • Author(s)
      相崎英樹、原弘道、森川賢一、宮村達男、脇田隆字、鈴木哲朗
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      ホテルグランパシフィックメリディアン
    • Year and Date
      20070531-0601
  • [Presentation] Infection and replication of hepatitis C virus2007

    • Author(s)
      脇田隆字
    • Organizer
      アジア太平洋消化器病週間 Asian Pacific Digestive Week 2007サテライトシンポジウム
    • Place of Presentation
      神戸商工会議所会館
    • Year and Date
      2007-10-17
  • [Presentation] C型肝炎のウイルス培養系の開発とその応用2007

    • Author(s)
      脇田隆字
    • Organizer
      第43回肝形態科学研究会
    • Place of Presentation
      ホテルグランパシフィックメリディアン
    • Year and Date
      2007-05-30
  • [Book] Isolation of JFH-1 strain and development of an HCV infection system. In : Hepatitis C Methods and Protocols Second Edition (ed. by Hengli Tan) Methods Mol Biol.2009

    • Author(s)
      Wakita T.
    • Total Pages
      305-27
    • Publisher
      Human Press
  • [Book] Development of an Infectious HCV Cell Culture System. In : Hepatitis C Viruses Genomes and Molecular Biology (ed. by Tan, S -L.)2006

    • Author(s)
      Kato T and Wakita T.
    • Total Pages
      451-464
    • Publisher
      Horizon Bioscience

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Published: 2010-06-10   Modified: 2012-09-10  

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