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

Research Project

Project/Area Number 15KK0291
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionHokkaido University

Principal Investigator

TSUDA YOSHIMI  北海道大学, 医学研究院, 講師 (70447051)

Project Period (FY) 2016 – 2019
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Keywordsウイルス / 病原性 / ウィルス / 感染症
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.

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。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2017 2016

All Int'l Joint Research (1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] 国立衛生研究所・ロッキーマウンテン研究所(米国)2016

    • Year and Date
      2016-10-27
    • Related Report
      2019 Annual Research Report
  • [Presentation] The role of viral replication in macrophages for pathogenesis of Ebola virus infection2017

    • Author(s)
      Yoshimi Tsuda, Shelly Robertson, Kimberly Meade-White, Brandi Williamson, Jiro Arikawa, Sonja Best, Hideki Ebihara
    • Organizer
      9th International Symposium on Filoviruses
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of viral tropism in macrophages in pathogenesis of Ebola virus disease2017

    • Author(s)
      Yoshimi Tsuda, Shelly Robertson, Kimberly Meade-White, Brandi Williamson, Jiro Arikawa, Sonja Best, Hideki Ebihara
    • Organizer
      The 65th Annual meeting of the Japanese society of Virology
    • Related Report
      2017 Research-status Report

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Published: 2016-10-04   Modified: 2021-02-19  

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