2022 Fiscal Year Final Research Report

Elucidation of neuroinvasive mechanism of rabies street viruses by using cutting-edge imaging techniques

Research Project

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Project/Area Number	18KK0192
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research Institution	Gifu University
Principal Investigator	Ito Naoto 岐阜大学, 応用生物科学部, 教授 (20334922)
Co-Investigator(Kenkyū-buntansha)	山田健太郎宮崎大学, 農学部, 准教授 (70458280) 佐々木道仁北海道大学, 人獣共通感染症国際共同研究所, 講師 (70609403) 西山祥子岐阜大学, 応用生物科学部, 助教 (90817058) 西園晃大分大学, 医学部, 教授 (70218155)
Project Period (FY)	2018-10-09 – 2023-03-31
Keywords	狂犬病ウイルス / 野外株 / 末梢感染
Outline of Final Research Achievements	In this study, with the goal of developing a prophylactic agent, which can supplement or replace rabies vaccine, we aimed to elucidate the importance and roles of rabies virus P protein isoforms P2-5 in the peripheral infection of the field strains We generated P2-5-deficient strains of the 1088 and Komatsugawa strains, respectively, by viral gene manipulation and examined their propagation and virulence (peripheral infectivity); the 1088-deficient strain showed decreased propagation and virulence, whereas the Komatsugawa-deficient strain showed no significant changes in these properties. Generation of the 1088 strain for in vivo imaging was attempted, but a significant decrease in its growth was observed due to an unexplained problem. Detailed examinations to optimize conditions for 3D tissue imaging using the uDISCO method also will be needed.
Free Research Field	獣医学
Academic Significance and Societal Importance of the Research Achievements	本研究で得られた成績は、今後、より詳細な検討が必要ではあるものの、狂犬病ウイルス野外株の病原性（末梢感染性）におけるP2-5アイソフォーム重要性はウイルス株ごとに異なることが示唆された。このことより、P2-5アイソフォームを標的として、どんなウイルス株にも対応可能な狂犬病予防薬を開発することは困難である可能性が高い。今後は、別のウイルス蛋白質を標的とした予防薬の開発にリソースを注ぐことが望ましいと判断できた。