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The role of lipid metabolism on HCV proliferation

Research Project

Project/Area Number 22249012
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionResearch Institute, International Medical Center of Japan (2012-2013)
Chiba Institute of Technology (2010-2011)

Principal Investigator

SHIMOTOHNO Kunitada  独立行政法人国立国際医療研究センター, その他部局等, その他 (10000259)

Project Period (FY) 2010-05-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥46,670,000 (Direct Cost: ¥35,900,000、Indirect Cost: ¥10,770,000)
Fiscal Year 2013: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2012: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2011: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2010: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Keywordsウイルス / 感染症 / C型肝炎ウイルス / 脂質 / 癌 / リポ蛋白質 / 持続感染 / VLDL受容体 / アポリポ蛋白質E / 低酸素環境 / VLDLR / LDLR / 感染 / 受容体 / 脂肪滴 / 脂肪症 / アポリポ蛋白質 / 複製
Research Abstract

Patients with chronic hepatitis C often develop steato-hepatitis. Abnormality of liver metabolism, often caused by activation of liver metabolism, in HCV infected liver is high, but roles of such the high metabolic activation in the cells in regards to virus proliferation remains elusive. We analyzed the role of lipid as well as its metabolism on HCV production and found; (1) HCV core protein is involved in accumulation of lipid droplet in the infected cells, (2) HCV associates with lipoprotein component(s) which is important for virus infectivity, (3) in particular, apolipoprotein E (Apo-E) plays an important roles in virus infectivity, (4) lipoprotein lipase treatment abolished virus infectivity possibly by dissociation of Apo-E from virus particle, (5) HCV infectivity is influenced by Apo-E isoforms; Apo-E3 and –E4 isoforms show high infectivity and Apo-E2 low. We also found a new lipoprotein receptor, VLDLR, for HCV entry.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (42 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (29 results) (of which Peer Reviewed: 10 results) Presentation (8 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The J6JFH1 Strain of Hepatitis C Virus Infects Human B-Cells with Low Replication Efficacy2014

    • Author(s)
      Nakai M, Seya T, Matsumoto M, Shimotohno K, Sakamoto N, Aly HH
    • Journal Title

      Viral Immunol

    • Related Report
      2013 Final Research Report
  • [Journal Article] Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection2014

    • Author(s)
      Tsugawa Y, Kato H, Fujita T, Shimotohno K, Hijikata M
    • Journal Title

      PLoS One

      Volume: 9(2)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Thromboxane A2 Synthase Inhibitors Prevent Production of Infectious Hepatitis C Virus in Mice With Humanized Livers2013

    • Author(s)
      Abe Y, Aly HH, Hiraga N, Imamura M, Wakita T, Shimotohno K, Chayama K, Hijikata M
    • Journal Title

      Gastroenterology

      Volume: 145 Pages: 658-667

    • Related Report
      2013 Final Research Report
  • [Journal Article] Hepatitis C Virus Infection Induces Inflammatory Cytokines and Chemokines Mediated by the Cross Talk between Hepatocytes and Stellate Cells2013

    • Author(s)
      Nishitsuji H, Funami K, Shimizu Y, Ujino S, Sugiyama K, Seya T, Takaku H, Shimotohno K
    • Journal Title

      J. Viol

      Volume: 87 Pages: 8169-8178

    • Related Report
      2013 Final Research Report
  • [Journal Article] PML tumor suppressor protein is required for HCV production2013

    • Author(s)
      Kuroki M, Ariumi Y, Hijikata M, Ikeda M, Dansako H, Wakita T, Shimotohno K, Kato N.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 430(2) Pages: 592-597

    • Related Report
      2013 Final Research Report
  • [Journal Article] Thromboxane A2 Synthase Inhibitors Prevent Production of Infectious Hepatitis C Virus in Mice with Humanized Livers.2013

    • Author(s)
      Abe Y, Aly HH, Hiraga N, Imamura M, Wakita T, Shimotohno K, Chavama K, Hijikata M.
    • Journal Title

      Gastroenterology

      Volume: 145 Issue: 3 Pages: 658-667

    • DOI

      10.1053/j.gastro.2013.05.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C Virus Infection Induces Inflammatory Cytokines and Chemokines Mediated by the Cross Talk between Hepatocytes and Stellate Cells.2013

    • Author(s)
      Nishitsuji H, Funami K, Shimizu Y, Ujino S, Sugiyama K, Seya T, Takaku H, Shimotohno K.
    • Journal Title

      J. Viol

      Volume: 87 Issue: 14 Pages: 8169-8178

    • DOI

      10.1128/jvi.00974-13

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different mechanisms of hepatitis C virus RNA polymerase activation by cyclophilin A and B in vitro2012

    • Author(s)
      Weng L, Tian X, Gao Y, Watashi K, Shimotohno K, Wakita T, Kohara M, Toyoda T
    • Journal Title

      Biochim Biophys Acta

      Volume: 1820(12) Pages: 1886-1892

    • Related Report
      2013 Final Research Report
  • [Journal Article] Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis2012

    • Author(s)
      Hirata Y, Ikeda K, Sudoh M, Tokunaga Y, Suzuki A, Weng L, Ohta M, Tobita Y, Okano Ozeki K, Kawasaki K, Tsukuda T, Katsume A, Aoki Y, Umehara T, Sekiguchi S, Toyoda T, Shimotohno K, Soga T, Nishijima M, Taguchi R, Kohara M
    • Journal Title

      PLoS Pathog

      Volume: 8(8)

    • Related Report
      2013 Final Research Report
  • [Journal Article] In vitro models for analysis of the hepatitis C virus life cycle2012

    • Author(s)
      Aly HH, Shimotohno K, Hijikata M, Seya T
    • Journal Title

      Microbiol Immunol

      Volume: 56(1) Pages: 1-9

    • Related Report
      2013 Final Research Report
  • [Journal Article] The interaction between human initiation factor eIF3 subunit c and heat-shock protein 90 : a necessary factor for translation mediated by the hepatitis C virus internal ribosome entry site2012

    • Author(s)
      Ujino S, Nishitsuji H, Sugiyama R, Suzuki H, Hishiki T, Sugiyama K, Shimotohno K, Takaku H
    • Journal Title

      Virus Res

      Volume: 163(1) Pages: 390-395

    • Related Report
      2013 Final Research Report
  • [Journal Article] Detergent-induced activation of the hepatitis C virus genotype 1b RNA polymerase2012

    • Author(s)
      Weng L, Kohara M, Wakita T, Shimotohno K, Toyoda T
    • Journal Title

      Gene

      Volume: 496 Issue: 2 Pages: 79-87

    • DOI

      10.1016/j.gene.2012.01.044

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipoprotein components associated with hepatitis C virus is essential for virus infectivity2011

    • Author(s)
      Shimizu Y, Hishiki T, Ujino S, Sugiyama K, Funmi K, Shimotohno K
    • Journal Title

      Current Opinion in Virology

      Volume: 1 Pages: 19-26

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Journal Article] Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV)2011

    • Author(s)
      Aly HH, Oshiumi H, Shime H, Matsumoto M, Wakita T, Shimotohno K, Seya T
    • Journal Title

      PLoS One

      Volume: 6(6)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Dysregulation of IFN system can lead to poor response to pegylated interferon and ribavirin therapy in chronic hepatitis C2011

    • Author(s)
      Onomoto K, Morimoto S, Kawaguchi T, Toyoda H, Tanaka M, Kuroda M, Uno K, Kumada T, Matsuda F, Shimotohno K, Fujita T, Murakami Y
    • Journal Title

      PLoS One

      Volume: 6(5)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of hepatitis C virus (HCV) through their catalytic activities on HCV-associated lipoproteins2011

    • Author(s)
      Shimizu Y, Hishiki T, Sugiyama K, Ogawa K, Funami K, Kato A, Ohsaki Y, Fujimoto T, Takaku H, Shimotohno K
    • Journal Title

      Virology

      Volume: 407(1) Pages: 152-915

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B2011

    • Author(s)
      Morohashi K, Sahara H, Watashi K, Iwabata K, Sunoki T, Kuramochi K, Takakusagi K, Miyashita H, Sato N, Tanabe A, Shimotohno K, Kobayashi S, Sakaguchi K, Sugawara F
    • Journal Title

      PLoS One

      Volume: 6(4)

    • Related Report
      2013 Final Research Report
  • [Journal Article] The Progression of Liver Fibrosis Is Related with Overexpression of the miR-199 and 200 Families2011

    • Author(s)
      Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, Kosaka N, Ochiya T, Shimotohno K
    • Journal Title

      PLoS One

      Volume: 6(1)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms2011

    • Author(s)
      Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fujimoto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K
    • Journal Title

      J Virol

      Volume: 84(22) Pages: 12048-12057

    • Related Report
      2013 Final Research Report
  • [Journal Article] In vitro models for the analysis of HCV life cycle2011

    • Author(s)
      Aly HH, Shimotohno K, Hijikata M, Seya T
    • Journal Title

      Microbiol Immunol

      Volume: 56 Issue: 1 Pages: 1-9

    • DOI

      10.1111/j.1348-0421.2011.00403.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipoprotein components associated with hepatitis C virus is essential for virus infectivity2011

    • Author(s)
      Ujino S, Nishitsuji H, Sugiyama R, Suzuki H, Hishiki T, Sugiyama K, Shimotohno K, Takaku H
    • Journal Title

      Virus Res

      Volume: 163 Issue: 1 Pages: 390-395

    • DOI

      10.1016/j.virusres.2011.10.003

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different mechanisms of hepatitis C virus RNA polymerase activation by cyclophilin A and B in vitro2011

    • Author(s)
      Weng L, Tian X, shimotohno K, et al.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1820 Issue: 12 Pages: 1886-1892

    • DOI

      10.1016/j.bbagen.2012.08.017

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B2011

    • Author(s)
      Morohashi K, Sahara H, Watashi K, Iwabata K, Sunoki T, Kuramochi K, Takakusagi K, Miyashita H, Sato N, Tanabe A, Shimotohno K, Kobayashi S, Sakaguchi K, Sugawara F
    • Journal Title

      PLoS ONE

      Volume: 6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C2010

    • Author(s)
      Murakami Y, Tanaka M, Toyoda H, Hayashi K, Kuroda M, Tajima A, Shimotohno K
    • Journal Title

      BMC Med Genomics

      Volume: 3(1) Pages: 48-48

    • Related Report
      2013 Final Research Report
  • [Journal Article] Sphingomyelin activates hepatitis C virus RNA polymerase in a genotype-specific manner2010

    • Author(s)
      Weng L, Hirata Y, Arai M, Kohara M, Wakita T, Watashi K, Shimotohno K, He Y, Zhong J, Toyoda T
    • Journal Title

      J Virol

      Volume: 84(22) Pages: 11761-11770

    • Related Report
      2013 Final Research Report
  • [Journal Article] Combination therapy for hepatitis C virus with heat-shock protein 90 inhibitor 17-AAG and proteasome inhibitor MG1322010

    • Author(s)
      Ujino S, Yamaguchi S, Shimotohno K, Takaku H
    • Journal Title

      Antivir Chem Chemother

      Volume: 20(4) Pages: 161-167

    • Related Report
      2013 Final Research Report
  • [Journal Article] Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of hepatitis C virus(HCV)through their catalytic activities on HCV-associated lipoproteins.2010

    • Author(s)
      Shimotohno K(Shimizu Y)
    • Journal Title

      Virology

      Volume: 152 Pages: 152-915

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingomyelin activates hepatitis C virus RNA polymerase in a genotype-specific manner2010

    • Author(s)
      Shimotohno K(Weng L)
    • Journal Title

      J.Virology

      Volume: 84 Pages: 11761-11770

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic microRNA expression is associated with the response to interfer on treatment of chronic hepatitis C2010

    • Author(s)
      Shimotohno K(Murakami Y)
    • Journal Title

      BMC Med Genomics

      Volume: 3 Pages: 48-48

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] HCV感染培養肝細胞は肝星状細胞と共培養する事によりMIP-1 beta産生を誘導する2013

    • Author(s)
      西辻 裕紀、清水 裕子、宇治野 真之、舟見 健児、川上 志保、瀬谷 司、下遠野 邦忠
    • Organizer
      平成24年度 文部科学省新学術領域研究がん研究分野の特性等を踏まえた支援活動公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2013-01-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Augmented productions of inflammatory cytokines by novel mechanisms in HCV-infected liver2013

    • Author(s)
      Yuko Shimizu, Hironori Nishitsuji, Hiroyuki Murasawa, Kenji Funami, Tsukasa Seya, Saneyuki Ujino, Ritsuko Shina, Hiromi Yamamoto, Atsuko Tsukimoto, Kunitada Shimotohno
    • Organizer
      The 3rd international symposium on carcinogenic spiral and international symposium on tumor biology
    • Place of Presentation
      金沢
    • Year and Date
      2013-01-24
    • Related Report
      2013 Final Research Report
  • [Presentation] C型肝炎ウイルスによるAPOBEC1 mRNA安定化とIL-8産生2012

    • Author(s)
      清水 裕子、宇治野 真之、 西辻 裕紀、椎名 律子、山本 祐美、高久 洋、下遠野 邦忠
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] C型肝炎ウイルスによるAPOBEC1 mRNAの安定化2012

    • Author(s)
      清水 裕子、宇治野 真之、 西辻 裕紀、高久 洋、下遠野 邦忠
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-14
    • Related Report
      2013 Final Research Report
  • [Presentation] HCV感染肝細胞は肝星状細胞と共培養する事によりMIP-1 beta産生をあげる2012

    • Author(s)
      西辻 裕紀、舟見 健児、清水 裕子、宇治野 真之、山本 祐美、鈴木 律子、川上 志保、瀬谷 司、高久 洋、下遠野 邦忠
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Hepatitis C virus sustains the level of APOBEC12012

    • Author(s)
      Yuko SHIMIZU, Saneyuki UJINO, Hironori NISHITSUJI, Hiroshi TAKAKU and Kunitada SHIMOTOHNO
    • Organizer
      19th international symposium on hepatitis C virus and related virus
    • Place of Presentation
      ベネチア(イタリア)
    • Year and Date
      2012-10-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Hepatitis C virus sustains the level of AP0BEC1 19th international symposium on hepatitis C virus and related virus2012

    • Author(s)
      Shimizu Y, Nishitsuj i H, Shimotohno K, et al.
    • Organizer
      International symposium on hepatitis C virus and related virus
    • Place of Presentation
      Italia
    • Year and Date
      2012-10-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hepatitis C virus hijacks lipid metabolism for its proliferation ; likely underlying mechanisms for the development of hepatocellular carcinoma2011

    • Author(s)
      Shimizu Y, Ujino S, Funami K, Kunitada Shimotohno K
    • Organizer
      International Congress of Virologist
    • Place of Presentation
      Sapporo(北海道)
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Book] 腫瘍ウイルス(肝炎ウイルス) がん生物学イラストレイテッド2011

    • Author(s)
      宇治野真之, 杉山和夫, 下遠野邦忠
    • Publisher
      羊土社 東京
    • Related Report
      2013 Final Research Report
  • [Book] 肝胆膵(アークメディア)2011

    • Author(s)
      日紫喜隆行、清水裕子、宇治野真之、下遠野邦忠
    • Publisher
      HCV形成の場としての脂肪滴の役割と粒子放出
    • Related Report
      2011 Annual Research Report
  • [Book] C型肝炎ウイルス研究の新知見 医学のあゆみ2010

    • Author(s)
      下遠野 邦忠
    • Publisher
      医歯薬出版株式会社 東京
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.viral-oncology.jp/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗HCV 薬2012

    • Inventor(s)
      田中晴雄、下遠野邦忠, ほか
    • Industrial Property Rights Holder
      学校法人明星学苑
    • Industrial Property Number
      2012-268884
    • Filing Date
      2012-12-08
    • Related Report
      2013 Final Research Report

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Published: 2010-11-30   Modified: 2019-07-29  

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