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Association analysis between the suppression of interferon responsiveness by HBV infection and changes of gene expression in human hepatocytes

Research Project

Project/Area Number 17KK0194
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

Tsuge Masataka  広島大学, 自然科学研究支援開発センター, 助教 (50448263)

Project Period (FY) 2018 – 2019
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
KeywordsB型肝炎ウイルス / ウイルス動態 / ヒト肝細胞キメラマウス / 遺伝子発現解析 / ヒト肝細胞 / キメラマウス / インターフェロン
Outline of Final Research Achievements

Human hepatocyte chimeric mice were infected with hepatitis B virus and thier liver tissues were collected after sacrifice. Total RNA was extracted from the mouse livers and transcribed into cDNA. Then gene expression analyses were perfomred using these cDNA and gene expression profiles were compared between HBV-infected and non-infected mice. Resulting these analyses, we identified that similar viral kinetic pattern could be observed regardless to HBV clones and that pathways associated with immune responses, cell growth or apoptosis were significantly activated in human hepatocytes after HBV infection. Furthermore, we also identified that intracellular resposes by HBV infection were different among HBV genotypes.

Academic Significance and Societal Importance of the Research Achievements

年間50万人以上がB型肝炎ウイルス感染により死亡するとされ、特にアジア地域ではその感染者数が多い。そのため、B型慢性肝炎に対する治療薬の開発は急務であり、現在、治療薬開発に向けた研究が進められ、新規治療薬の登場が期待されている。このような背景から、治療薬開発において、抗ウイルス効果が評価可能な動物モデルの作製は非常に重要であり、また本研究のようなウイルス動態の視点から評価も必須と言える。本研究を進めていくことで、B型肝炎治療に向けた治療標的が同定され、本研究で得られた遺伝子発現プロファイルが新規治療薬開発の基盤として活用できる可能性がある。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2019 2018

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Int'l Joint Research] Loyola university Chicago(米国)2018

    • Year and Date
      2018-07-23
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP2019

    • Author(s)
      Makokha Grace Naswa、Abe-Chayama Hiromi、Chowdhury Sajeda、Hayes C. Nelson、Tsuge Masataka、Yoshima Tadahiko、Ishida Yuji、Zhang Yizhou、Uchida Takuro、Tateno Chise、Akiyama Rie、Chayama Kazuaki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 8462-8462

    • DOI

      10.1038/s41598-019-44934-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヒト肝細胞キメラマウスを用いたB型肝炎研究の最前線2019

    • Author(s)
      柘植雅貴、茶山一彰
    • Journal Title

      消化器・肝臓内科

      Volume: 6 Pages: 271-278

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Early Multiphasic HBV Infection Initiation Kinetics Is Not Clone-Specific and Is Not Affected by Hepatitis D Virus (HDV) Infection2019

    • Author(s)
      Tsuge Masataka, Uchida Takuro, Walsh Kevin, Ishida Yuji, Tateno Chise, Kumar Upendra, Glenn Jeffrey, Koh Christopher, Heller Theo, Uprichard Susan, Dahari Harel, Chayama Kazuaki
    • Journal Title

      Viruses

      Volume: 11 Issue: 3 Pages: 263-263

    • DOI

      10.3390/v11030263

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of intracellular responses between HBV genotype A and C infection in human hepatocyte chimeric mice2019

    • Author(s)
      Tsushima K, Tsuge M, Hiraga N, Uchida T, Murakami E, Makokha GN, Kurihara M, Nomura Motonobu, Hiyama Y, Fujino H, Ono A, Nakahara T, Yamauchi M, Abe-Chayama H, Kawaoka T, Miki D, Imamura M, Aikata H, Hayes CN, Chayama K
    • Journal Title

      Journal of Gastroenterology

      Volume: 印刷中 Issue: 7 Pages: 650-659

    • DOI

      10.1007/s00535-019-01558-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CTL-associated and NK cell-associated immune responses induce different HBV DNA reduction patterns in chronic HBV infection.2019

    • Author(s)
      Masataka Tsuge, Motonobu Nomura, Takuro Uchida, Hiromi Abe-Chayama, Daiki Miki, Michio Imamura, Hiroshi Aikata, Grace Naswa Makokha, C. Nelson Hayes, Kazuaki Chayama
    • Organizer
      7th Japan-Taiwan-Korea HBV Research Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核酸アナログ・ペグインターフェロン併用療法におけるHBs低下に寄与する因子の検討2019

    • Author(s)
      柘植雅貴、辰川裕美子、茶山一彰
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 症例から学ぶ B型肝炎の診断・治療の最前線2019

    • Author(s)
      柘植雅貴
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Analysis of the association between HBV infection and long-term trends in intrahepatic gene expression.2019

    • Author(s)
      Masataka Tsuge, Ken Tsushima, Nobuhiko Hiraga, Takuro Uchida, Michio Imamura, C. Hayes Nelson, Harel Dahari, Susan L. Uprichard, Kazuaki Chayama
    • Organizer
      International HBV meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Investigation of infectivity of serum-derived HBV from patients and human hepatocyte chimeric mouse to HepG2/NTCP cells.2019

    • Author(s)
      Hatsue Fujino, Miko Namba, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Hiromi Abe-Chayama, C. Hayes Nelson, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama
    • Organizer
      International HBV meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serum atutotaxin levels is useful to evaluate fibrosis during entecavir therapy and to predict the development of hepatocellular carcinoma in patients with chronic hepatitis B.2019

    • Author(s)
      Hatsue Fujino, Kei Morio, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Hiromi Abe-Chayama, C. Hayes Nelson, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama
    • Organizer
      International HBV meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核酸アナログ・ペグインターフェロン併用療法におけるHBs低下に寄与する因子の検討2019

    • Author(s)
      藤野初江、柘植雅貴、寺岡雄吏、盛生慶、大野敦司、中原隆志、村上英介、河岡友和、三木大樹、平松憲、今村道雄、相方浩、茶山一彰
    • Organizer
      第43回日本肝臓学会西部会
    • Related Report
      2019 Annual Research Report

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Published: 2018-01-25   Modified: 2022-06-09  

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