| Project/Area Number |
17K08866
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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 | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 幸枝 福井大学, 学術研究院医学系部門, 助教 (10197486)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥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 / インフラマソーム / IL-1β / アクセサリー蛋白質 / 自然免疫 / NLRP3インフラマソーム / ウイルス |
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| Outline of Final Research Achievements |
SeV V protein inhibited the assembly of NLRP3 inflammasomes, including NLRP3-dependent ASC oligomerization, NLRP3-ASC association, NLRP3 self oligomerization, and intermolecular interactions between NLRP3 molecules. Moreover, a high correlation between the NLRP3-binding capacity of V protein and the ability to block inflammasome complex assembly was observed. Therefore, SeV V protein likely inhibits NLRP3 self-oligomerization by interacting with NLRP3 and inhibiting subsequent recruitment of ASC to block NLRP3-dependent ASC oligomerization, in turn blocking full activation of the NLRP3 inflammasome and thus blocking IL-1beta secretion. Notably, the inhibitory action of SeV V protein on NLRP3 inflammasome activation is shared by other paramyxovirus V proteins, such as Nipah virus and human parainfluenza virus type 2. We thus reveal a mechanism by which paramyxovirus inhibits inflammatory responses by inhibiting NLRP3 inflammasome complex assembly and IL-1beta activation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって，複数のパラミクソウイルス（マウスパラインフルエンザウイルス1型，ニパウイルス，ヒトパラインフルエンザウイルス2型）のV蛋白質に抗ウイルス免疫に重要なインフラマソームの活性化を抑制する能力が保存されていることが明らかになった． V蛋白質は多くのパラミクソウイルスに保存されているため，幅広いパラミクソウイルスの予防法や治療薬の標的になると考えられた．
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