| Project/Area Number |
26460553
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Gotoh Bin 滋賀医科大学, 医学部, 教授 (00211920)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | パラミクソウイルス / インターフェロン / IFNアンタゴニスト / アクセサリー蛋白質 / 自然免疫 / TLR7/9 |
|---|
| Outline of Final Research Achievements |
Human metapneumovirus is a member of the family Paramyxoviridae, and its M2-2 protein has the ability to inhibit TLR7/9 dependent signaling pathway leading to alpha interferon production by plasmacytoid dendritic cells. However, detailed molecular mechanism for the inhibition remained unclear. Here we found that the M2-2 protein interacted with IRF7, and inhibited IRF7 homodimerization induced by stimulation of the TLR7/9 pathway. In contrast to this inhibition, interaction of the M2-2 protein with IRF7 did not result in inhibition of IRF7 homodimerization induced by stimulation of the RIG-I/MDA5 pathway, suggesting that the inhibition of homodimerization is not caused by steric effect of the M2-2 binding. Instead, M2-2 was found to inhibit phosphorylation of IRF7 on Ser477. These results suggest that M2-2 blocks the TLR7/9 pathway by inhibiting IRF7 homodimerization possibly through inhibition of its serine phosphorylation.
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