Molecular mechanism for the inhibition of TLR7/9-dependent signaling pathway by human metapneumovirus.
| 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 |
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| 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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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Intramolecular complementation of measles virus fusion protein stability confers cell-cell fusion activity at 37 °C.2015
Author(s)
Satoh, Y., Hirose, M., Shogaki, H., Wakimoto, H., Kitagawa, Y., Gotoh, B., Takahashi, K. and Itoh, M.
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Journal Title
FEBS Lett.
Volume: 589
Issue: 1
Pages: 152-158
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Functional roles of the hemagglutinin protein of a Subacute sclerosis pan encephalitis (SSPE) virus, the Kobe-1 strain2016
Author(s)
Yuto Satoh, Daichi Nishikawa, Kurara Higuchi, Da-Peng Jiang, Hiroko Shougaki, Hiroshi Wakimoto, Yoshinori Kitagawa, Bin Gotoh, Ken-ichi Takahashi, Hak Hotta, and Masae Itoh
Organizer
日本ウイルス学会
Place of Presentation
北海道札幌市
Year and Date
2016-10-23
Related Report
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[Presentation] 麻疹ウイルスF蛋白質のHR-B領域内465位アミノ酸による膜融合活性調節機構2015
Author(s)
Hiroko shogaki, Yuto Satoh, Saeka Yonemori, Mitsuhiro Hirose, Hiroshi Wakimoto, Yoshinori Kitagawa, Bin Gotoh, Ken-ichi Takahashi, Masae Itoh
Organizer
日本ウイルス学会学術集会
Place of Presentation
福岡市
Year and Date
2015-11-22
Related Report
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