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Host lipids that regulate the function of replication factories of RNA viruses

Research Project

Project/Area Number 17H05070
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

YAMANE Daisuke  公益財団法人東京都医学総合研究所, 疾患制御研究分野, 主席研究員 (60782761)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywordsウイルス / 感染症 / 脂質 / RNAウイルス / 複製複合体 / 脂質代謝 / 脂肪酸 / 小胞体膜 / 宿主因子
Outline of Final Research Achievements

Positive strand RNA viruses initiate genome replication within specialized membrane vesicles, designated "replication factory", in infected cells. Such organelles are typically induced by engagement of viral proteins and associated with morphological changes in the structure of host internal membranes. Whereas the process involved in formation of the replication factory must involve alterations in host lipid metabolism, the mechanistic details remain poorly characterized. Through investigations by means of microarray analysis, comprehensive lipidomics analysis and fatty acid profiling, this study has revealed that RNA viruses modulate cellular lipid profiles via modulation of cellular phospholipase activity that cleaves fatty acid tails from membrane phospholipids as well as fatty acid desaturases. Importantly, analyses of fatty acid metabolic pathways that catalyze fatty acid cleavage or desaturation identified host targets that could lead to development of virus-specific antivirals.

Academic Significance and Societal Importance of the Research Achievements

ウイルス感染特異的に変化する脂質代謝を理解することはウイルスの感染・複製機構の解明のみならず、その代謝経路を標的とすることでウイルス特異的に作用する創薬に繋がる。この研究において、異なるウイルス感染によって普遍的および特異的に誘導される脂質代謝変化を包括的に捉えたことにより、脂肪酸代謝の重要性を見出すことに繋がった。また、脂肪酸代謝を標的とする薬剤がウイルス複製を有意に変化させることを見出したことから、脂肪酸代謝酵素が抗ウイルス薬の標的分子となり得ることを実証できた。この研究から得られた成果をもとに、今後動物感染モデルを用いた試験を通じて、より安全性の高い創薬開発へと発展することが期待できる。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (15 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (5 results) (of which Invited: 2 results) Remarks (2 results)

  • [Int'l Joint Research] The University of North Carolina(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Interferon regulatory factor 1 (IRF1) and anti-pathogen innate immune responses2021

    • Author(s)
      Feng Hui、Zhang Yi-Bing、Gui Jian-Fang、Lemon Stanley M.、Yamane Daisuke
    • Journal Title

      PLOS Pathogens

      Volume: 17 Issue: 1 Pages: e1009220-e1009220

    • DOI

      10.1371/journal.ppat.1009220

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extended interaction networks with HCV protease NS3-4A substrates explain the lack of adaptive capability against protease inhibitors2020

    • Author(s)
      Dultz Georg、Shimakami Tetsuro、Schneider Markus、Murai Kazuhisa、Yamane Daisuke、Marion Antoine、Zeitler Tobias M.、Stross Claudia、Grimm Christian、Richter Rebecca M.、B?umer Katrin、Yi MinKyung、Biondi Ricardo M.、Zeuzem Stefan、Tamp? Robert、Antes Iris、Lange Christian M.、Welsch Christoph
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 40 Pages: 13862-13874

    • DOI

      10.1074/jbc.ra120.013898

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Basal expression of interferon regulatory factor 1 drives intrinsic hepatocyte resistance to multiple RNA viruses2019

    • Author(s)
      Yamane D, Feng H, Rivera-Serrano EE, Selitsky SR, Hirai-Yuki A, Das A, McKnight KL, Misumi I, Hensley L, Lovell W, González-López O, Suzuki R, Matsuda M, Nakanishi H, Ohto-Nakanishi T, Hishiki T, Wauthier E, Oikawa T, Morita K, Reid LM, Sethupathy P, Kohara M, Whitmire JK, Lemon SM
    • Journal Title

      Nature Microbiology

      Volume: 印刷中 Issue: 7 Pages: 1096-1104

    • DOI

      10.1038/s41564-019-0425-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatovirus 3ABC proteases and evolution of mitochondrial antiviral signaling protein (MAVS)2019

    • Author(s)
      Feng Hui、Sander Anna-Lena、Moreira-Soto Andr?s、Yamane Daisuke、Felix Drexler Jan、Lemon Stanley M.
    • Journal Title

      Journal of Hepatology

      Volume: in press Issue: 1 Pages: 25-34

    • DOI

      10.1016/j.jhep.2019.02.020

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication2019

    • Author(s)
      Hishiki Takayuki、Kato Fumihiro、Nio Yasunori、Watanabe Satoru、Wen Tan Nicole Wei、Yamane Daisuke、Miyazaki Yasuyuki、Lin Chun-Chieh、Suzuki Rieko、Tajima Shigeru、Lim Chang-Kweng、Saijo Masayuki、Hijikata Makoto、Vasudevan Subhash G.、Takasaki Tomohiko
    • Journal Title

      Antiviral Research

      Volume: 165 Pages: 42-46

    • DOI

      10.1016/j.antiviral.2019.03.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains.2017

    • Author(s)
      Benzine T, Brandt R, Lovell WC, Yamane D, Neddermann P, De Francesco R, Lemon SM, Perelson AS, Ke R, McGivern DR.
    • Journal Title

      PLoS Pathog.

      Volume: 13 Issue: 6 Pages: e1006343-e1006343

    • DOI

      10.1371/journal.ppat.1006343

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NLRX1 promotes immediate IRF1-directed antiviral responses by limiting dsRNA-activated translational inhibition mediated by PKR.2017

    • Author(s)
      Feng H, Lenarcic EM, Yamane D, Wauthier E, Mo J, Guo H, McGivern DR, Gonzalez-Lopez O, Misumi I, Reid LM, Whitmire JK, Ting JP, Duncan JA, Moorman NJ, Lemon SM.
    • Journal Title

      Nat Immunol.

      Volume: 18 Issue: 12 Pages: 1299-1309

    • DOI

      10.1038/ni.3853

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脂溶性ビタミンを介した肝炎ウイルス複製制御機構2020

    • Author(s)
      山根大典
    • Organizer
      第364回脂溶性ビタミン総合研究委員会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 肝細胞に内在するRNA ウイルス抑制シグナルとその制御機構2020

    • Author(s)
      山根大典
    • Organizer
      第65回肝炎ウイルスセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] RARRES3 mediates interferon regulatory factor 1-induced suppression of hepatitis A virus replication through modulation of the mTOR activity.2019

    • Author(s)
      Daisuke Yamane, Asuka Hirai-Yuki, Michinori Kohara, Stanley M. Lemon
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MAVS-independent activity of interferon regulatory factor 1 restricts hepatotropic RNA virus infections2018

    • Author(s)
      Daisuke Yamane, Asuka Hirai-Yuki, Ichiro Misumi, Michinori Kohara, Jason K Whitmire, and Stanley M Lemon
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Efficient replication of non-adapted hepatitis C virus isolates in cell culture2017

    • Author(s)
      Daisuke Yamane, Michinori Kohara
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Remarks] ウイルス感染を抑制する新たな肝細胞の自然免疫の仕組みを発見

    • URL

      http://www.igakuken.or.jp/topics/2019/0415.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] How Liver Cells Protect Against Viral Attacks

    • URL

      https://globalhealth.unc.edu/2019/04/researchers-identify-liver-cells-protect-viral-attacks/

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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