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Elucidation of the amplification mechanism using cultured human prion persistent infection cells and development of novel prevention and treatment for prion diseases

Research Project

Project/Area Number 18H02721
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Atarashi Ryuichiro  宮崎大学, 医学部, 教授 (90452846)

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, グループ長補佐 (20355142)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsプリオン病 / RT-QuIC法 / PMCA法 / 孤発性クロイツフェルトヤコブ病 / 異常型PrP / クロイツフェルト・ヤコブ病 / 培養細胞 / RT-QUIC法 / クロイツフェルトヤコブ病 / 異常型プリオンタンパク質
Outline of Final Research Achievements

The objectives of this study were (1) to elucidate the mode of infection of cultured cells with human prion and the mechanism of persistent infection, and (2) to develop a system for spontaneous prion generation using recombinant prion protein derived from insect cells. After analyzing the growth characteristics and other properties of cultured cells that were used in this study, we verified whether the cells could be infected with human prion persistently. In (2), multiple prion variants were spontaneously generated by the reaction at 45 degrees Celsius, but the variants lost their characteristics and converged to a single one after the reaction repeated. This study clarified the disappearance process of human prion in cultured cells and the mechanism of spontaneous generation of multiple prion variants and their competing processes.

Academic Significance and Societal Importance of the Research Achievements

プリオン病は致死性の神経変性疾患で病理像の異なる複数の変異株が存在する。現時点ではプリオン病に対する有効な予防・治療法は存在せず、その開発が切実に求められている。孤発性や遺伝性プリオン病では生体内で自発的に異常型プリオンタンパクが生じ、生体内で増幅するが、その分子機構の詳細は不明である。本研究により、ヒトプリオンの培養細胞への持続感染成立の条件と自発生成機構の解明につながる研究成果を得ることができ、現在それらの知見を活かした予防・治療法の開発を目指し、研究活動を継続している。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (7 results)

All 2022 2021 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RT-QuIC as ultrasensitive method for prion detection.2022

    • Author(s)
      Atarashi R.
    • Journal Title

      Cell Tissue Res.

      Volume: - Issue: 1 Pages: 295-300

    • DOI

      10.1007/s00441-021-03568-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] 異常型プリオンタンパク無細胞増幅法(RT-QUIC法とPMCA法)を駆使したプリオン病病態機構の解明.2021

    • Author(s)
      新竜一郎
    • Organizer
      第25回日本神経感染症学会総会・学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] さまざまなリコンビナントプリオン蛋白を基質としたRT-QUIC法の反応性の比較解析2019

    • Author(s)
      森剛志, 今村守一, 高月英恵, 井口洋美, 大野美奈子, 新竜一郎
    • Organizer
      日本ウイルス学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Isolation of hidden minor prion conformers from classical scrapie isolates in advanced protein misfolding cyclic amplification in the presence of arginine ethyl ester.2019

    • Author(s)
      Imamura M, Miyazawa K, Matsuura Y, Iwamaru Y, Kitamoto T, Mohri S, Takatsuki H, Mori T, Atarashi R
    • Organizer
      Asian Pacific Prion Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pentosan polysulfate induces latent prion infection in Fukuoka-1 strain-infected cells.2019

    • Author(s)
      Takatsuki H, Mori T, Imamura M, Atarashi R
    • Organizer
      Asian Pacific Prion Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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