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Quality and evolutionary control of RNA virus genome via nonsense mediated mRNA decay

Research Project

Project/Area Number 22K20759
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0803:Pathology, infection/immunology, and related fields
Research InstitutionKyoto University

Principal Investigator

Komorizono Ryo  京都大学, 医生物学研究所, 特定助教 (10964637)

Project Period (FY) 2022-08-31 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsウイルス学 / ウイルス進化 / RNAウイルス / RNA分解
Outline of Research at the Start

ヒトを含む真核生物には突然変異などによって本来より上流に終止コドンが出現してしまった不良なmRNAを探知し、選択的に分解するRNAの品質管理システムが存在する。近年、このナンセンス変異依存mRNA分解機構(NMD)は内在性RNAだけでなくRNAウイルスに対しても作用すると明らかとなった。NMDは変異によって生じる異常なRNAを選択的に探知・分解するという観点から、この機構はRNA分解を介してウイルス進化にも影響を与える進化制御機構であると仮説を立てた。本研究では、このRNA品質機構であるNMDが急性感染性ならびに持続感染性RNAウイルスの進化を左右するかNGSによりゲノム配列を詳細に解析する。

Outline of Final Research Achievements

To analyze the interaction between viral infection and host NMD mechanisms, several gene knockdown cells were established with lentiviral vectors, including the UPFs, SMGs, and G3BP1 genes, which are key factors of NMD pathway. Inoculation of these cells with the RNA viruses Borna disease virus and coxsackie virus B3 (CVB3) resulted in significantly increased viral RNA amounts in the supernatant and infected cells. Similarly, NMDI-14, an NMD inhibitor, significantly increased viral RNA levels in each infected cell as well as in the knockdown cells. These results suggest that the host NMD mechanism or each key factor has antiviral activity to inhibit RNA virus replication.

Academic Significance and Societal Importance of the Research Achievements

本研究ではNMD機構がRNAウイルスの複製を制御していることが明らかとなったことから、NMD機構、特にUPFやSMG遺伝子を標的とした抗ウイルス薬の開発に貢献すると期待できる。またNMDとウイルス感染の相互作用の詳細はいまだ未解明であるが、RNAウイルスが感染に利用する新たな宿主機構として知見を得た意義のある成果といえる。本研究で用いたCVB3においては、ある特定の細胞種では細胞傷害性なしに長期間子孫粒子を産生する持続感染を成立させることが明らかとなり、急性感染と持続感染を1つのウイルス種で並行して解析できる実験系を確立させたことは本研究のみならず今後のウイルス学研究に活用されると予想される。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (11 results)

All 2024 2023 2022

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

  • [Journal Article] Contact-number-driven virus evolution: A multi-level modeling framework for the evolution of acute or persistent RNA virus infection2023

    • Author(s)
      Sunagawa Junya、Komorizono Ryo、Park Hyeongki、Hart William S.、Thompson Robin N.、Makino Akiko、Tomonaga Keizo、Iwami Shingo、Yamaguchi Ryo
    • Journal Title

      PLOS Computational Biology

      Volume: 19 Issue: 5 Pages: 1011173-1011173

    • DOI

      10.1371/journal.pcbi.1011173

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reverse genetics of parrot bornavirus 4 reveals a unique splicing of the glycoprotein gene that affects viral propagation2023

    • Author(s)
      Komorizono Ryo、Fujino Kan、Kessler Susanne、Runge Solveig、Kanda Takehiro、Horie Masayuki、Makino Akiko、Rubbenstroth Dennis、Tomonaga Keizo
    • Journal Title

      Journal of Virology

      Volume: 97 Issue: 8 Pages: 00509-00509

    • DOI

      10.1128/jvi.00509-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution2023

    • Author(s)
      Sunagawa Junya、Park Hyeongki、Kim Kwang Su、Komorizono Ryo、Choi Sooyoun、Ramirez Torres Lucia、Woo Joohyeon、Jeong Yong Dam、Hart William S.、Thompson Robin N.、Aihara Kazuyuki、Iwami Shingo、Yamaguchi Ryo
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 7395-7395

    • DOI

      10.1038/s41467-023-43043-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Excel-REGENS: The ex vivo gene cell therapy using REVec-based genetically engineered stem cells.2023

    • Author(s)
      Ryo Komorizono, Shima Yoshizumi, Keizo Tomonaga
    • Organizer
      第70回日本ウイルス学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ボルナウイルスベクターを用いた遺伝子細胞治療薬の開発2023

    • Author(s)
      Ryo Komorizono
    • Organizer
      第29回日本遺伝子細胞治療学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] RNA Virus Based Episomal Vector for Highly Efficient Genetic Engineering of Human Mesenchymal Stromal Cells2023

    • Author(s)
      Ryo Komorizono, Shima Yoshizumi, Miya Kawanaka, Keizo Tomonaga
    • Organizer
      American Society of Gene & Cell Therapy The 26th Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己複製型RNAウイルスベクター「REVec」の応用2023

    • Author(s)
      小森園亮
    • Organizer
      BioJapan2023
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of an RNA virus-based episomal vector with artificial aptazyme for switching gene expression off2022

    • Author(s)
      Ryo Komorizono, Chiaki Tanaka, Shima Yoshizumi, Keizo Tomonaga
    • Organizer
      第23回日本RNA学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Intranuclear viral RdRp of Borna disease virus 1 interferes with host RNA maturation and metabolism.2022

    • Author(s)
      Miina Kaneko, Ryo Komorizono, Akiko Makino, Keizo Tomonaga
    • Organizer
      第20回あわじ感染と免疫国際フォーラム
    • Related Report
      2022 Research-status Report
  • [Presentation] Product of a human endogenous bornavirus-like element suppresses RNA interference in mammalian cells2022

    • Author(s)
      Ryo Komorizono, Miya Kawanaka, Shima Yoshizumi, Keizo Tomonaga
    • Organizer
      第69回日本ウイルス学会
    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] ボルナウイルスベクターを利用した細胞の遺伝子改変と当該細胞を用いた細胞治療薬2024

    • Inventor(s)
      小森園亮、朝長啓造
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2024
    • Related Report
      2023 Annual Research Report

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Published: 2022-09-01   Modified: 2025-01-30  

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