the study of pathogenicity of Ebola virus disease using reverse genetics system(Fostering Joint International Research)

2019 Fiscal Year Final Research Report

• Project/Area Number: 15KK0291
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: TSUDA YOSHIMI 北海道大学, 医学研究院, 講師 (70447051)
• Project Period (FY): 2016 – 2019
• Keywords: ウイルス / 病原性

Outline of Final Research Achievements

Cells of the mononuclear phagocyte system (MPS) such as macrophages and dendritic cells are early targets for Ebola virus (EBOV) infection. However, the pathobiological significance of EBOV replication to these cells is remaining unclear. Cellular tropism of viruses can be engineered through the insertion of cell-specific target sequences for microRNA in the viral genome. Using this mechanism, we generated recombinant mouse-adapted EBOV possessing a microRNA target sequence (MAEBOV-t) that microRNA is expressed predominantly in the MPS cells and evaluated pathogenicity of MAEBOV-t in mice model. MAEBOV-t showed significantly attenuated pathogenicity in infected mice. Analysis of virus propagation and immune response in infected mice suggest that efficient inhibition of virus replication in the first target cells suppress virus propagation in tissues as well as immune responses, resulting enabled to induce effective immune response for survival.

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ヒトやサルに重篤な出血熱を引き起こす人獣共通感染症である。2014年の大規模なアウトブレイク以後、ワクチンや治療薬の開発が進んでいるが、有効な治療薬や的確な対症療法の開発のための病原性の解明は喫緊の課題である。本研究の成果は、エボラウイルスの初期標的細胞とされていたマクロファージや樹状細胞での感染初期におけるウイルス増殖がその後の致死的病態にどのように関与し、宿主応答を誘導するかを示すものであり、メカニズム解明への一助となるとともに、今後の治療法開発などに非常に重要な知見を与えるものとなると考えられる。