Elucidation of our recent findings on the protective role of prion protein against lethal infection with influenza A viruses is useful for development of a new type of anti-influenza drugs
| Project/Area Number |
15K15380
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Infectious disease medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SAKAGUCHI Suehiro 徳島大学, 先端酵素学研究所(次世代), 教授 (60274635)
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| Co-Investigator(Kenkyū-buntansha) |
矢野 雅司 徳島大学, 先端酵素学研究所(次世代), 技術専門職員 (10531858)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | プリオン蛋白質 / インフルエンザ / インフルエンザウイルス / 活性酸素種 / 銅イオン / 銅/亜鉛依存性スーパーオキシドジスムターゼ / ノックアウトマウス / アポトーシス / 酸化ストレス / 抗体 / リード化合物 |
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| Outline of Final Research Achievements |
Here we show that the cellular prion protein, PrPC, is expressed in lung epithelial cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) developed higher mortality after infection with influenza A viruses (IAVs). Infected Prnp0/0 lungs were severely injured, with higher apoptosis of the epithelial cells, and contained higher ROS than control WT lungs. Treatment with a ROS scavenger rescued Prnp0/0 mice from the lethal infection with IAV. These results indicate that PrPC provides a protection against lethal infection with IAVs by reducing ROS in infected lungs. Cu contents and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu contents and regulate SOD1 in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting from lethal infection with IAVs, suggesting that PrPC might be a new target for anti-influenza therapeutics.
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Report
(3 results)
Research Products
(4 results)
