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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02721
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: University 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
• 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

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.

Free Research Field

微生物学

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。