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Studies on host factors regulating HIV-1 replication

Research Project

Project/Area Number 18K07143
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Yamaoka Shoji  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (90263160)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsHIV / host factor / Vpu / BST-2 / Lentiviral vector / SPSB1 / Tax / ヒト免疫不全ウイルス / 宿主因子 / 進化 / サル免疫不全ウイルス / SIV / GSN / 複製 / 遺伝子ライブラリー / アクセサリータンパク質 / レンチウイルスベクター / ウイルス / ゲノムワイドスクリーン
Outline of Final Research Achievements

Three papers have been published in international journals describing virus-host interaction. A cellular factor SPSB1 was found to enhance proviral expression. This led to a discovery that SPSB1 and HTLV-I-derived trans-activator Tax potently enhance lentiviral production. Patz1 was identified as an important cellular factor essentially involved in reverse transcription through an expression cloning with a human T-cell line MT4 and cDNA expression library. The Vpu protein of SIVgsn71 was found to interact with human BST-2 through their membrane-spanning regions and downregulate cell surface expression of human BST-2, which facilitated HIV-1 virion release in the presence of human BST-2.

Academic Significance and Societal Importance of the Research Achievements

HIVプロウイルスの発現を促進する細胞因子はホルボールエステル等の転写活性化因子が知られているが、これをレンチウイルスベクターの産生増強に応用した初めての研究成果であり、その発展的展開はCAR-T治療等に使われるレンチウイルスベクターの産生に多大な貢献をすることが期待される。Patz1の同定はそのウイルス学的意義にとどまらず、演繹的な方法では発見が困難なウイルス複製促進因子の同定における発現クローニングの威力を示すもので、方法論的に意義深い。サル免疫不全ウイルスのVpuがヒトBST-2を発現抑制しうることの発見は、種を越えて感染進化するウイルスと宿主の相互関係を理解する上で大きな意義がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019 2018 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] Vpu of a Simian Immunodeficiency Virus Isolated from Greater Spot-Nosed Monkey Antagonizes Human BST-2 via Two AxxxxxxxW Motifs2020

    • Author(s)
      Yao W, Yoshida T, Hashimoto S, Takeuchi H, Strebel K, Yamaoka S.
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 2

    • DOI

      10.1128/jvi.01669-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PATZ1 is required for efficient HIV-1 infection2019

    • Author(s)
      Aziati ID, Yoshida T, Hamano A, Maeda K, Takeuchi H, Yamaoka S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 514 Issue: 2 Pages: 538-544

    • DOI

      10.1016/j.bbrc.2019.04.175

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis2019

    • Author(s)
      Asakawa M, Itoh M, Suganami T, Sakai T, Kanai S, Shirakawa I, Yuan X, Hatayama T, Shimada S, Akiyama Y, Fujiu K, Inagaki Y, Manabe I, Yamaoka S, Yamada T, Tanaka S, Ogawa Y.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 19601-19601

    • DOI

      10.1038/s41598-019-56039-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] eIF4A2 is a host factor required for efficient HIV-1 replication2018

    • Author(s)
      Ndzinu Jerry Kwame、Takeuchi Hiroaki、Saito Hideki、Yoshida Takeshi、Yamaoka Shoji
    • Journal Title

      Microbes and Infection

      Volume: 20 Issue: 6 Pages: 346-352

    • DOI

      10.1016/j.micinf.2018.05.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robust Enhancement of Lentivirus Production by Promoter Activation2018

    • Author(s)
      Suzuki Naoto、Yoshida Takeshi、Takeuchi Hiroaki、Sakuma Ryuta、Sukegawa Sayaka、Yamaoka Shoji
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1

    • DOI

      10.1038/s41598-018-33042-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Two Isoforms of PATZ1 are Required for Efficient HIV-1 Infection2020

    • Author(s)
      Ishmael Aziati, Takeshi Yoshida, Hiroaki Takeuchi, Jacco Boon, Kenjiro Maeda and Shoji Yamaoka
    • Organizer
      American Society for Virology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ウイルスの宿主適応メカニズム:宿主防御機構とのせめぎ合いと攻略能獲得まで2020

    • Author(s)
      芳田剛、Weitong Yao、橋本紗希、武内寛明、山岡昇司
    • Organizer
      エイズ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Enhancement of Lentivirus Production by Inducing Promoter Activation2019

    • Author(s)
      Naoto Suzuki, Takeshi Yoshida, Hiroaki Takeuchi, Ryuta Sakuma, Sayaka Sukegawa, Shoji Yamaoka
    • Organizer
      日本ウイルス学会
    • Related Report
      2019 Research-status Report
  • [Presentation] HIV-1は抗ウイルスタンパク質ヒトBST-2に拮抗する機能をどのように獲得したのか2019

    • Author(s)
      Weitong Yao、芳田剛、橋本紗希、武内寛明、山岡昇司
    • Organizer
      日本エイズ学会
    • Related Report
      2019 Research-status Report
  • [Presentation] An SIV Vpu can antagonize human BST-2/tetherin2018

    • Author(s)
      Takeshi Yoshida,Weitong Yao,Saki Hashimoto,Hiroaki Takeuchi,Shoji Yamaoka
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Endogenous activation of BST-2 by CRISPR reduces HIV-1 replication2018

    • Author(s)
      Kenzo Tokunaga,Yanzhao Zhang,Seiya Ozono,Weitong Yao,Minoru Tobiume,Shoji Yamaoka,Satoshi Kishigami,Hideaki Fujita
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Identification of a host factor supporting HIV-1 entry2018

    • Author(s)
      Takeshi Yoshida, Saki Kawamura, Haruka Yamaguchi, Hiroaki Takeuchi, Shoji Yamaoka
    • Organizer
      第32回日本エイズ学会
    • Related Report
      2018 Research-status Report
  • [Presentation] HIV 潜伏感染を制御する宿主因子の同定および解析2018

    • Author(s)
      武内寛明, 合田仁, 石田尚臣, 佐藤賢文, 岩瀬早織, 山岡昇司
    • Organizer
      第32回日本エイズ学会
    • Related Report
      2018 Research-status Report
  • [Remarks] 研究テーマ

    • URL

      http://molv.org/research.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] レンチウイルスベクターの産生を飛躍的に増大させる方法を開発

    • URL

      http://www.tmd.ac.jp/archive-tmdu/kouhou/20181011_1.pdf

    • Related Report
      2018 Research-status Report
  • [Remarks] レンチウイルスベクターの産生を飛躍的に増大させる方法を開発

    • URL

      https://www.amed.go.jp/news/release_20181011-02.html

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] レンチウイルスベクター産生の増強方法2021

    • Inventor(s)
      山岡 昇司: 鈴木 尚人: 芳田 剛
    • Industrial Property Rights Holder
      山岡 昇司: 鈴木 尚人: 芳田 剛
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-549114
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] レンチウイルスベクター産生の増強方法2019

    • Inventor(s)
      山岡昇司、芳田剛、鈴木尚人
    • Industrial Property Rights Holder
      山岡昇司、芳田剛、鈴木尚人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] レンチウイルスベクター産生の増強方法2018

    • Inventor(s)
      山岡昇司、 鈴木尚人、芳田剛
    • Industrial Property Rights Holder
      山岡昇司、 鈴木尚人、芳田剛
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-176230
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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