Characterization of molecular mechanism of distribution of phospholipid in Ebola virus particles

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Nagasaki University (2019-2020); Hokkaido University (2018)
• Principal Investigator: NANBO Asuka 長崎大学, 感染症共同研究拠点, 教授 (60359487)
• Co-Investigator(Kenkyū-buntansha): 津田 祥美 北海道大学, 医学研究院, 講師 (70447051)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エボラウイルス / ウイルス粒子形成 / リン脂質 / エキソサイトーシス / エンドサイトーシス / 生体膜輸送

Outline of Final Research Achievements

Ebola virus produces virus particles with long filamentous morphology from the plasma membrane. VP40 serves as a viral major matrix protein, which associates with inner layer of the plasma membrane and leads to the virion formation and budding. In normal cells, the integrity of the plasma membrane is tightly regulated by homeostatic balance between exocytosis and endocytosis. The viral particle producing cells maintain the normal cell size nevertheless the filamentous particles constitutively bud from the cell surface acquiring their lipid bilayer, suggesting the unknown mechanism for maintenance of plasma membrane homeostasis. Here, by applying various microscopic approaches, we identified the novel functions of VP40 in upregulation of the plasma membrane-directed vesicle trafficking followed by subsequent exocytosis and in blockage of clathrin-mediated endocytosis, leading to the compensation of lipid bilayers in addition to the trafficking of VP40 itself to the plasma membrane.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

エボラウイルス病は、高い致死率を伴う重篤な疾病であるにも関わらず、治療法が極めて限られている。既存のエボラウイルス感染阻害薬は、主にウイルス侵入とゲノム複製を標的にしたものであり、ウイルス粒子形成を標的とした薬剤は未開発である。従って、本研究を、ウイルス粒子形成を標的とした新規阻害薬の探索へと展開することで、将来的なエボラウイルスの制圧に貢献することが期待される。