2016 Fiscal Year Final Research Report
Investigation of pathogenetic mechanism of Ebola virus disease using reverse genetics system
| Project/Area Number |
26860297
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | Hokkaido University |
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Principal Investigator |
Tsuda Yoshimi 北海道大学, 医学研究科, 助教 (70447051)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | ウイルス / 病原性 |
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| Outline of Final Research Achievements |
Cells of the mononuclear phagocyte system, such as macrophages/monocytes, are the primary target cells of Ebola virus (EBOV). To investigate the pathological significance of targeted infection of macrophages/monocytes by EBOV, we generated recombinant EBOV possessing the target sequences of microRNA (EBOV-miRt) that is expressed in hematopoietic cells. We first characterized the replication of EBOVs in the human hepatoma cells as well as the macrophage-derived cells. Compared with control EBOV, EBOV-miRt showed reduced replication in only macrophage-derived cells. To analyze the role of macrophages/monocytes in pathogenesis, mice were inoculated with mouse-adapted-EBOV-miRt or control mouse-adapted-EBOV. Mice infected with mouse-adapted-EBOV-miRt survived. Conversely, mice inoculated with mouse-adapted-EBOV succumbed to infection. These results suggested that replication in macrophages is an important factor contributing to a lethal outcome of EBOV infection.
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| Free Research Field |
ウイルス学
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