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2013 Fiscal Year Final Research Report

Impact of hepatitis C virus infection in B cells on pathogenesis

Research Project

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Project/Area Number 23590547
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionKagoshima University

Principal Investigator

KOHARA Kyoko  鹿児島大学, 獣医学部, 教授 (20225478)

Project Period (FY) 2011 – 2013
KeywordsC型肝炎ウイルス / Bリンパ腫 / microarray / A20 / NF-kB / miR-26b
Research Abstract

Hepatitis C virus (HCV) infection leads to the development of hepatic diseases, as well as extra hepatic disorders such as B-cell non-Hodikin's lymphoma (B-NHL). To reveal the molecular signaling pathways responsible for HCV-associated B-NHL development, we utilized transgenic (Tg) mice that express the full-length HCV genome specifically in B cells and develop non-Hodgkin type B-cell lymphomas (BCLs). The gene expression profiles in B cells from BCL-developing HCV-Tg mice, from BCL-non-deceloping HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analyzed by genome-wide microarray.
Markedly modified genes such as Fos, C3, LTbR, A20, NF-kB and miR-26b in BCLs were further characterized using specific assays. We propose that activation of both canonical and alternative NF-kB signaling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.

  • Research Products

    (30 results)

All 2014 2013 2012 2011 Other

All Journal Article (17 results) Presentation (6 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling2014

    • Author(s)
      Kasama Y, Mizukami T, Kusunoki H, Peveling-Oberhag J, Nishito Y, Ozawa M, Kohara M, Mizuochi T, Tsukiyama-Kohara K
    • Journal Title

      PLoS One

      Volume: 9(3) Pages: e91373

    • DOI

      10.1371/journal.pone.0091373

  • [Journal Article] Recent insights into hepatitis B virus-host interactions2014

    • Author(s)
      Ezzikouri S, Ozawa M, Kohara M, Elmdaghri N, Benjelloun S, Tsukiyama-Kohara K
    • Journal Title

      J Med Virol

      Volume: 86(6) Pages: 925-32

    • DOI

      10.1002/jmv.23916

  • [Journal Article] A serine palmytoiltransferase inhibitor inhibits hepatitis C virus replication in human hepatocytes2013

    • Author(s)
      Katsume A, Tokunaga Y, Hirata Y, Munakata T, Saito M, Hayashi H, Okamoto Y, Kusanagi I, Fujiwara S, Klumpp K, Tsukiyama-Kohara K, El-Gohary A, Sudoh M, Kohara M
    • Journal Title

      Gastroenterology

      Volume: 145(4)(pii : S0016-5085(13)00914-1. 10.1053) Pages: 865-73

  • [Journal Article] 4E-BP1 regulates the differentiation of white adipose tissue2013

    • Author(s)
      Tsukiyama-Kohara K, Katsume A, Kimura K, Saito M, Kohara M
    • Journal Title

      Genes Cells

      Volume: 18(7) Pages: 602-607

    • DOI

      10.1111/gtc.12059

  • [Journal Article] Targeted induction of interferon-λin humanized chimeric mouse liver abrogates hepatotropic virus infection2013

    • Author(s)
      Nakagawa S, Hirata Y, Kameyama T, Tokunaga Y, Nishito Y, Hirabayashi K, Yano J, Ochiya T, Tateno C, Tanaka Y, Mizokami M, Tsukiyama-Kohara K, Inoue K, Yoshiba M, Takaoka A, Kohara M
    • Journal Title

      PLoS One

      Volume: 8(3) Pages: e59611

    • DOI

      10.1371/journal.pone.0059611

  • [Journal Article] Genomic polymorphisms in 3β-hydroxysterolΔ24-reductase promoter sequences2013

    • Author(s)
      Salem NE, Saito M, Kasama Y, Ozawa M, Kawabata T, Harada S, Suda H, Asonuma K, El-Gohary A, Tsukiyama-Kohara K
    • Journal Title

      Microbiol Immunol

      Volume: 57(3) Pages: 179-184

    • DOI

      10.1111/1348-0421.12025

  • [Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppr esses viral protein levels in mouse liver2012

    • Author(s)
      Sekiguchi S, Kimura K, Chiyo T, Ohtsuki T, Tobita Y, Tokunaga Y, Yasui F, Tsukiyama-Kohara K, Wakita T, Tanaka T, Miyasaka M, Mizuno K, Hayashi Y, Hishima T, Matsushima K and Kohara M
    • Journal Title

      Pros One

      Volume: 7(12) Pages: e51656

    • DOI

      10.1371/journal.pone.0051656

  • [Journal Article] Role of Oxidative stress in hepatocarcinogenesis induced by hepatitis C virus2012

    • Author(s)
      Tsukiyama-Kohara K
    • Journal Title

      Int J Mol Sci

      Volume: 13 Pages: 15271-15278

    • DOI

      10.3390/ijms131115271

  • [Journal Article] Impairment of interferon regulatory factor-3 activation by hepatitis C virus core protein basic amino acid region 12012

    • Author(s)
      Inoue K, Tsukiyama-Kohara K, Matsuda C, Yoneyama M, Fujita T, Kuge S, Yoshiba M, and Kohara M
    • Journal Title

      Biochem Biophys Res Com

      Volume: 428(4) Pages: 494-499

    • DOI

      10.1016/j.bbrc.2012.10.079

  • [Journal Article] Hepatitis C virus promotes expression of the 3β-hydroxysterolΔ24-reductase through Sp12012

    • Author(s)
      Saito M, Kohara M, Tsukiyama-Kohara K
    • Journal Title

      J Med Virol

      Volume: 84 (5) Pages: 733-746

    • DOI

      10.1002/jmv.23250

  • [Journal Article] Translocase of outermitochondrial membrane 70 induces interferon response and is impaired by hepatitis C virus NS32012

    • Author(s)
      Kasama Y, Saito M, Takano T, Nishimura T, Satoh M, Wang Z, Ali S.N. E. S., Harada S, Kohara M, Tsukiyama-Kohara K
    • Journal Title

      Virus Research

      Volume: 163 Pages: 405-409

    • DOI

      10.1016/j.virusres.2011.10.009

  • [Journal Article] Selective translation of the measles virus nucleocapsid mRNA by la protein2011

    • Author(s)
      Inoue Y, Sato H, Fujita K, Tsukiyama-Kohara K, Yoneda M, Kai C
    • Journal Title

      F ront Microbiol

      Volume: 2 Pages: 173

    • DOI

      10.3389/fmicb.2011.00173

  • [Journal Article] Monoclonal antibody 2-152a suppresses hepatitis C virus infection thorough betaine/GABA transporter-12011

    • Author(s)
      Satoh M, Saito M, Takano T, Kasama Y, Nishimura T, Nishito Y, Hirata Y, Arai M, Sudoh M, Kai C, Kohara M and Tsukiyama-Kohara K
    • Journal Title

      J Infect Dis

      Volume: 204(8) Pages: 1172-1180

    • DOI

      10.1093/infdis/jir501

  • [Journal Article] Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes2011

    • Author(s)
      Takano T, Tsukiyama-Kohara K, Hayashi M, Hirata Y, Satoh M, Tateno C, Hayashi Y, Hishima T, Funata N, Sudo M, and Kohara M
    • Journal Title

      J Hepatology

      Volume: 55(3) Pages: 512-521

    • DOI

      10.1016/j.jhep.2010.12.011

  • [Journal Article] Translocase of outer mitochondrial membrane 70 expression is induced by hepatitis C virus and is related to the apoptotic response2011

    • Author(s)
      Takano T, Kohara M, Kasama Y, Nishimura T, Saito M, Kai C and Tsukiyama-Kohara K
    • Journal Title

      J Med Virol

      Volume: 83 Pages: 801-809

    • DOI

      10.1002/jmv.22046

  • [Journal Article] Hepatitis C virus-related lymphomagenesis in a mouse model2011

    • Author(s)
      Tsukiyama-Kohara K, Sekiguchi S, Kasama Y, Salem NE, Machida K, Kohara M
    • Journal Title

      ISRN Hemato

      Volume: 2011 Pages: 167501

    • DOI

      10.5402/2011/167501

  • [Journal Article] Potential of a recombinant measles virus as expression vector of hepatitis C virus envelope proteins2011

    • Author(s)
      Kasama Y, Satoh M, Saito M, Okada S, Kai C, and Tsukiyama-Kohara K
    • Journal Title

      World J Vaccine

      Volume: 1 Pages: 98-103

    • DOI

      10.4236/wjv.2011.13010

  • [Presentation] Tumorigenicity induced by hepatitis C virus2014

    • Author(s)
      Tukiyama-Kohara K, Kohara M
    • Organizer
      第4回新学術領域発がんスパイラル国際シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2014-02-11
  • [Presentation] 型肝炎ウイルス誘導性酸化ストレスによる肝細胞腫瘍原性更新2013

    • Author(s)
      小原恭子
    • Organizer
      第24回日本生体防御学会
    • Place of Presentation
      熊本
    • Year and Date
      2013-07-12
  • [Presentation] Chronic hepatitis C virus model in Tupaia belangeri2013

    • Author(s)
      Tsukiyama-Kohara K, Amako Y, Kohara M
    • Organizer
      SIMPOSIUM"HCV animal models and vaccine development"
    • Place of Presentation
      Tallinn, Estonia
    • Year and Date
      2013-05-17
  • [Presentation] Inflammation and cancer in hepatitis C virus infection2013

    • Author(s)
      Tsukiyama-Kohara K, Kimuara K, Kohara M
    • Organizer
      3rd IGAKUKEN International Symposium on Control of Influenza and Hepatitis
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-02-15
  • [Presentation] Inflammation and Cancer in Hepatitis C virus Infection2012

    • Author(s)
      Tsukiyama-Kohara K, Kimuara K, Kohara M
    • Organizer
      International symposium : Infection, immunity and cancer
    • Place of Presentation
      Kyoto
    • Year and Date
      2012-01-17
  • [Presentation] C型肝炎ウイルス誘発性リンパ腫モデルマウスの樹立と解析2011

    • Author(s)
      笠間由里
    • Organizer
      第7回麒麟塾
    • Place of Presentation
      東京
    • Year and Date
      2011-06-04
  • [Book] 新時代のウイルス性肝炎学, 日本臨床69巻増刊4別刷, HCVの病原性発現に関与するウイルス因子とその機能II C型肝炎C型肝炎ウイルス感染における免疫応答と感染防御機構2011

    • Author(s)
      小原恭子、棟方翼、小原道法
    • Total Pages
      97-102
  • [Book] BIO Clinica 26 (10), C型肝炎ウイルスによる免疫攪乱と炎症発がん2011

    • Author(s)
      小原道法、小原恭子
    • Total Pages
      42-48
  • [Book] 肝臓, 疾患モデルマウス:表現型解析指南2011

    • Author(s)
      小原恭子、小原道法
    • Total Pages
      188-192
    • Publisher
      中山書店
  • [Remarks]

    • URL

      http://www.vet.kagoshima-u.ac.jp/kadai

  • [Patent(Industrial Property Rights)] C型肝炎の予防、治療又は改善用組成物2011

    • Inventor(s)
      小原恭子、松森昭、西村 知裕、小原道法
    • Industrial Property Rights Holder
      国立大学法人熊本大学、松森昭、(一般財団法人)化学及血清療法研究所、(公財)東京都医学研究機構
    • Industrial Property Number
      特願2011-125440
    • Filing Date
      2011-06-03
  • [Patent(Industrial Property Rights)] C型肝炎ウイルス阻害剤

    • Inventor(s)
      小原恭子、小原道法 他
    • Industrial Property Rights Holder
      (一般財団法人)化学及血清療法研究所、(公財) 東京都医学研究機構、国立大学法人熊本大学
    • Industrial Property Number
      12/241868
    • Overseas
  • [Patent(Industrial Property Rights)] Hepatitis C virus inhibitors

    • Inventor(s)
      小原恭子、小原道法 他
    • Industrial Property Rights Holder
      (一般 財団法人)化学及血清療法研究所、(公財) 東京都医学研究機構、国立大学法人熊本大学
    • Industrial Property Number
      CA2640954
    • Overseas

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Published: 2015-07-16  

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