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Elucidation of the origin of typical bovine spongiform encephalopathy

Research Project

Project/Area Number 21K05938
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Imamura Morikazu  宮崎大学, 医学部, 准教授 (10391442)

Co-Investigator(Kenkyū-buntansha) 岩丸 祥史  国立研究開発法人農業・食品産業技術総合研究機構, 動物衛生研究部門, グループ長 (20355142)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsプリオン / BSE / PMCA / 試験管内増幅 / 牛海綿状脳症
Outline of Research at the Start

本研究は従来型牛海綿状脳症(定型BSE)の起源を明らかにすることを目的とする。研究には、PMCAと呼ばれる試験管内でプリオンを増幅できる技術を用いる。まず、定型BSEが反芻動物間の異種間伝達により生じた可能性を探るため、様々な反芻動物プリオンをシードとし、異種反芻動物プリオン蛋白質を基質としてPMCAを行い、定型BSEプリオンが生じるかを調べる。また、定型BSEは孤発的に発生した可能性も否定できない。そこで、牛組換えプリオン蛋白質を基質としたシードプリオンを加えないPMCA法により牛組換えプリオンを自発生成させ、定型BSEプリオンの性状と比較することで孤発的発生の可能性を検討する。

Outline of Final Research Achievements

In this study, experiments to mimic prion transmission between heterologous animals and to examine spontaneous prion production were conducted using the PMCA method, an in vitro amplified prion amplification method, with the aim of clarifying the origin of the canonical BSE. As a result, in vitro amplification of multiple animal prions using heterologous normal prion protein (PrPC) as a substrate yielded prion-like products. Bioassays of some of these products showed that they were infectious to mice. Furthermore, PMCA using recombinant bovine PrP as a substrate without prion seed yielded recombinant prions that were infectious to bovine-expressing transgenic mice. Further detailed analysis of the properties of the generated prions is needed in the future.

Academic Significance and Societal Importance of the Research Achievements

定型BSEの起源については未だ十分な科学的根拠が得られておらず未解明のままである。定型BSEプリオンがどのように出現したかを明らかにすることで、国内のBSE発生防止対策の改善ならびに見直しに資する重要な科学的知見が得られ、定型BSEの再流行を阻止する効果的な方策が可能となるさらに、定型BSEプリオンが生み出される機序を明らかにすることで、プリオンが自発発生する機構の解明につながると考える。

Report

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

    (4 results)

All 2023 2022

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

  • [Journal Article] Spontaneous generation of distinct prion variants with recombinant prion protein from a baculovirus-insect cell expression system2022

    • Author(s)
      Imamura M, Tabeta N, Iwamaru Y, Takatsuki H, Mori T, Atarashi R.
    • Journal Title

      Biochem Biophys Res Commun .

      Volume: 613 Pages: 67-72

    • DOI

      10.1016/j.bbrc.2022.04.137

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pentosan polysulfate induces low-level persistent prion infection keeping measurable seeding activity without PrP-res detection in Fukuoka-1 infected cell cultures2022

    • Author(s)
      Takatsuki H, Imamura M, Mori T, Atarashi R.
    • Journal Title

      Sci Rep.

      Volume: - Issue: 1 Pages: 7923-7923

    • DOI

      10.1038/s41598-022-12049-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Demonstration of multiple prion conformers in natural scrapie isolates by PMCA2023

    • Author(s)
      Morikazu Imamura
    • Organizer
      Asian Pacific Prion Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] H-BSE prions adapted to ovine PrP in vitro acquired C-BSE-like properties.2022

    • Author(s)
      Morikazu Imamura, Hiroyuki Okada, Kotaro Miyazawa, Yuichi Matsuura, Yoshifumi Iwamaru, Hanae Takatsuki, Tsuyoshi Mori, Ryuichiro Atarashi
    • Organizer
      Asian Pacific Prion Symposium 2022
    • Related Report
      2022 Research-status Report

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

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