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Establishment of control methods for Borna disease virus, an emerging risk

Research Project

Project/Area Number 21K07053
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Makino Akiko  京都大学, 医生物学研究所, 准教授 (30571145)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsエマージングリスク / 人獣共通感染症 / ボルナ病ウイルス / 抗ウイルス化合物 / RNA / ウイルス
Outline of Research at the Start

ボルナ病ウイルスはヒトに病原性をほとんど示さないと考えられてきたが、臓器移植による伝播をきっかけに致死性脳炎を起こすことが明らかになった。しかし同ウイルス特異的な治療法は確立されていない。申請者はこれまでに化合物ライブラリのハイスループットスクリーニングにより、抗ボルナ病ウイルス活性を示す化合物を同定した。本研究では、エマージングリスクであるボルナ病ウイルスによる致死性脳炎の制御法の確立を目的として、同定した抗ウイルス化合物の作用機序の解明、脳炎モデルでの疾患マーカーの同定と制御法の確立をおこなう。本研究はボルナ病ウイルスによる致死性脳炎の診断法および治療法の開発に貢献するものと考えられる。

Outline of Final Research Achievements

The objective of this study was to develop a method for controlling lethal encephalitis caused by Borna disease virus, an emerging risk. To this end, the mechanisms of action of antiviral compounds were elucidated and their antiviral effects were evaluated. Screening identified 11 candidate compounds, among which Compound 4 exhibited the strongest antiviral activity. Compound 4 was suggested to be involved in the intracellular entry process of the Borna disease virus and to target the M gene. The findings of this study contribute to the development of therapeutics for Borna disease virus and provide a foundation for preparedness in the event of potential new infectious disease risks.

Academic Significance and Societal Importance of the Research Achievements

本研究では、エマージングリスクであるボルナ病ウイルスによる致死性脳炎を抑制する新規抗ウイルス化合物を発見し、その作用機序を解明した。この成果により、ボルナ病ウイルス感染症の効果的な治療法開発が期待される。社会的には、新たな感染症リスクへの備えとして重要である。学術的には、ウイルスの感染メカニズムの解明に貢献し、今後の研究基盤を強化した。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (18 results)

All 2024 2023 2022 2021

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] Predicted risk of heart failure pandemic due to persistent SARS-CoV-2 infection using a three-dimensional cardiac model2024

    • Author(s)
      Murata Kozue、Makino Akiko、Tomonaga Keizo、Masumoto Hidetoshi
    • Journal Title

      iScience

      Volume: 27 Issue: 1 Pages: 108641-108641

    • DOI

      10.1016/j.isci.2023.108641

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] Efficacy of oligodendrocyte precursor cells as delivery vehicles for single-chain variable fragment to misfolded SOD1 in ALS rat model2023

    • Author(s)
      Minamiyama Sumio、Sakai Madoka、Yamaguchi Yuko、Kusui Makiko、Wada Hideki、Hikiami Ryota、Tamaki Yoshitaka、Asada-Utsugi Megumi、Shodai Akemi、Makino Akiko、Fujiwara Noriko、Ayaki Takashi、Maki Takakuni、Warita Hitoshi、Aoki Masashi、Tomonaga Keizo、Takahashi Ryosuke、Urushitani Makoto
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 28 Pages: 312-329

    • DOI

      10.1016/j.omtm.2023.01.008

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stability of Borna disease virus‐based episomal vector under physical and chemical stimulation2021

    • Author(s)
      Yanai Mako、Sakai Madoka、Komorizono Ryo、Makino Akiko、Tomonaga Keizo
    • Journal Title

      Microbiology and Immunology

      Volume: 66 Issue: 1 Pages: 24-30

    • DOI

      10.1111/1348-0421.12946

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] BUD23?TRMT112 interacts with the L protein of Borna disease virus and mediates the chromosomal tethering of viral ribonucleoproteins2021

    • Author(s)
      Garcia Bea Clarise B.、Horie Masayuki、Kojima Shohei、Makino Akiko、Tomonaga Keizo
    • Journal Title

      Microbiology and Immunology

      Volume: 65 Issue: 11 Pages: 492-504

    • DOI

      10.1111/1348-0421.12934

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Human Endogenous Bornavirus-Like Nucleoprotein Encodes a Mitochondrial Protein Associated with Cell Viability2021

    • Author(s)
      Fujino Kan、Horie Masayuki、Kojima Shohei、Shimizu Sae、Nabekura Aya、Kobayashi Hiroko、Makino Akiko、Honda Tomoyuki、Tomonaga Keizo
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 14

    • DOI

      10.1128/jvi.02030-20

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 核内複製RNAウイルスの翻訳制御機構2024

    • Author(s)
      牧野晶子
    • Organizer
      関西RNAクラブ
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ボルナ病ウイルス2型に検出される遺伝子多型の特性評価2023

    • Author(s)
      西岡慶一郎、神田雄大、朝長啓造、牧野晶子
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] SARS-CoV-2由来small RNAによるウイルス複製制御2023

    • Author(s)
      小野紘貴、橋本里菜、牧野晶子、高山和雄、朝長啓造、齊藤博英
    • Organizer
      第一回新型コロナウイルス研究集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Involvement of TRIM28/33 in SARS-CoV-2 replication.2022

    • Author(s)
      Madoka Sakai, Kosuke Yusa, Keizo Tomonaga, Akiko Makino.
    • Organizer
      第69回日本ウイルス学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Identification of a small compound that inhibits Borna disease virus 1 in vitro.2022

    • Author(s)
      Miina Kaneko, Madoka Sakai, Yukiko Okuno, Shinsuke Inuki, Keizo Tomonaga, Akiko Makino.
    • Organizer
      第69回日本ウイルス学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] CRISPR/CAS9 SCREENING FOR HOST FACTORS INVOLVED IN SARS-COV-2 INFECTION.2022

    • Author(s)
      Madoka Sakai, Kosuke Yusa, Keizo Tomonaga, Akiko Makino.
    • Organizer
      International Union of Microbiological Societies
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathogenicity of variegated squirrel bornavirus.2022

    • Author(s)
      Akiko Makino, Kan Fujino, Keizo Tomonaga
    • Organizer
      International Union of Microbiological Societies
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Host cellular machinery for SARS-CoV-2 infection2021

    • Author(s)
      牧野晶子
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] CRISPR/Cas9 システムを用いた重症急性呼吸器症候群コロナウイルス2感染に関わる宿主因子の同定2021

    • Author(s)
      酒井まどか、遊佐宏介、朝長啓造、牧野晶子
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ボルナ病ウイルスXタンパク質がウイルス感染サイクルに与える影響の解明2021

    • Author(s)
      神田雄大、小森園亮、牧野晶子、朝長啓造
    • Organizer
      第164回日本獣医学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Additional expression of matrix protein and glycoprotein facilitates infectious virus production of Borna disease virus 12021

    • Author(s)
      Takehiro Kanda, Madoka Sakai, Akiko Makino, Keizo Tomonaga
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Selection and characterization of persistent infectious variants of SARS-CoV-2 .2021

    • Author(s)
      Ryo Komorizono, Junna Kawasaki, Akiko Makino, Keizo Tomonaga
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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