Investigation of pathogenetic mechanism of Ebola virus disease using reverse genetics system
| Project/Area Number |
26860297
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
Tsuda Yoshimi 北海道大学, 医学研究科, 助教 (70447051)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | ウイルス / 病原性 / エボラウイルス / リバースジェネティクス / マクロファージ |
|---|
| 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.
|
Report
(4 results)
Research Products
(4 results)
