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Functional analysis of avSG-mediated antiviral innate immune signaling.

Research Project

Project/Area Number 19K07589
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionChiba University

Principal Investigator

Onomoto Koji  千葉大学, 真菌医学研究センター, 助教 (10612202)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsウイルス感染 / ストレス顆粒 / 自然免疫 / ウイルス / ストレス応答 / ウイルス学
Outline of Research at the Start

本研究計画では生化学・分子生物学・細胞生物学的に抗ウイルスストレス顆粒(antiviral stress granule:avSG)と呼ばれる細胞内凝集体を解析し、その生理的機能及び抗ウイルス自然免疫に関わる新規分子を同定し、抗ウイルス免疫応答の空間的制御メカニズムの解明と新規抗ウイルス治療薬や予防薬への開発につながる知見を見出すことを目的とする。

Outline of Final Research Achievements

In this study, we tried to understand the function of antiviral stress granule (avSG) in RLR-mediated innate immune response. avSGs are membrane-less cytoplasmic aggregates that serve as a platform for foreign viral RNAs by RLRs. However, the molecular function of avSG formations remains unclear in antiviral innate immunity. To elucidate the role of avSG, we identified several novel molecules that regulated avSG formations and RLR-mediated IFN signals using both in vivo and in vitro approaches. Moreover, we also investigated the role of avSG formations in SARS-CoV-2 infected cells.

Academic Significance and Societal Importance of the Research Achievements

近年、細胞内凝集体であるStress Granule(SG)が細胞の恒常性の維持やアルツハイマー病などの神経変性疾患にも関与していることが明らかになり、その形成制御機構が注目を集めている。本研究によりウイルスRNAにより形成されるSGを介した抗ウイルス免疫応答の制御機構がin vitro及びin vivoの双方から解明できれば、これまで内在性のRNAの機能制御に関与していると考えられていたSGが抗ウイルス自然免疫とクロストークしているという新たな抗ウイルス免疫制御機構を提示することができ、将来的なSGを標的とした抗ウイルス薬の開発につながる可能性もあり、非常に重要であると考えている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 2 results) Remarks (5 results)

  • [Journal Article] ヨウ素の新型コロナウイルス(SARS-CoV-2)不活化作用2022

    • Author(s)
      尾野本浩司, 米山光俊, 浅倉聡, 松本伸一, 海宝龍夫
    • Journal Title

      日本防菌防黴学会誌

      Volume: 50 Pages: 97-103

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis2021

    • Author(s)
      Hayashi Yushi、Suzuki Hidenori、Nakajima Wataru、Uehara Ikuno、Tanimura Atsuko、Himeda Toshiki、Koike Satoshi、Katsuno Tatsuya、Kitajiri Shin-ichiro、Koyanagi Naoto、Kawaguchi Yasushi、Onomoto Koji、Kato Hiroki、Yoneyama Mitsutoshi、Fujita Takashi、Tanaka Nobuyuki
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 11 Pages: e0260443-e0260443

    • DOI

      10.1371/journal.pone.0260443

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors2021

    • Author(s)
      Onomoto Koji、Onoguchi Kazuhide、Yoneyama Mitsutoshi
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 18 Issue: 3 Pages: 539-555

    • DOI

      10.1038/s41423-020-00602-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cochlear supporting cells function as macrophage-like cells and protect audiosensory receptor hair cells from pathogens2020

    • Author(s)
      Yushi Hayashi, Hidenori Suzuki, Wataru Nakajima, Ikuno Uehara, Atsuko Tanimura, Toshiki Himeda, Satoshi Koike, Tatsuya Katsuno, Shin-ichiro Kitajiri, Naoto Koyanagi, Yasushi Kawaguchi, Koji Onomoto, Hiroki Kato, Mitsutoshi Yoneyama, Takashi Fujita, Nobuyuki Tanaka
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 6740-6740

    • DOI

      10.1038/s41598-020-63654-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] LGP2 virus sensor enhances apoptosis by upregulating apoptosis regulatory genes through TRBP-bound miRNAs during viral infection.2020

    • Author(s)
      Takahashi T, Nakano Y, Onomoto K, Yoneyama M, Ui-Tei K.
    • Journal Title

      Nucleic Acids Res.

      Volume: 48 Issue: 3 Pages: 1494-1507

    • DOI

      10.1093/nar/gkz1143

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a new autoinhibitory domain of interferon-beta promoter stimulator-1 (IPS-1) for the tight regulation of oligomerization-driven signal activation2019

    • Author(s)
      Takahasi Kiyohiro、Onomoto Koji、Horiuchi Masataka、Kato Hiroki、Fujita Takashi、Yoneyama Mitsutoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 517 Issue: 4 Pages: 662-669

    • DOI

      10.1016/j.bbrc.2019.07.099

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Functional analysis of TRBP in RLR mediated antiviral innate immune signal2020

    • Author(s)
      Koji Onomoto, Miyu Watanabe, Tomoko Takahashi, Yuko Nakanao, Kumiko Ui-Tei, Mitsutoshi Yoneyama
    • Organizer
      The 8th Global Network Forum on Infection and Immunity
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The RIG-I like receptor LGP2 enhances apoptosis mediated by TRBP-bound miRNAs during viral infection.2020

    • Author(s)
      Tomoko Takahashi, Yuko Nakanao, Mitsutoshi Yoneyama, Koji Onomoto, Kumiko Ui-Tei
    • Organizer
      The 8th Global Network Forum on Infection and Immunity
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞内ウイルスセンサーLGP2はRNAサイレンシングを介してウイルス感染細胞の細胞死を制御する2019

    • Author(s)
      高橋朋子、中野悠子、尾野本浩司、米山光俊、程久美子
    • Organizer
      第21回日本RNA学会年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 千葉大学真菌医学研究センター ホームページ

    • URL

      http://www.pf.chiba-u.ac.jp/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 千葉大学真菌医学研究センター感染免疫分野 ホームページ

    • URL

      http://www.pf.chiba-u.ac.jp/project_immuneresponses/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 千葉大学真菌医学研究センター感染免疫分野

    • URL

      http://www.pf.chiba-u.ac.jp/project_immuneresponses/

    • Related Report
      2020 Research-status Report
  • [Remarks] 千葉大真菌医学研究センター

    • URL

      http://www.pf.chiba-u.ac.jp/research/project/yoneyama.html

    • Related Report
      2020 Research-status Report
  • [Remarks] 千葉大学真菌医学研究センター感染免疫分野

    • URL

      http://www.pf.chiba-u.ac.jp/project_immuneresponses/publication.html

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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