molecular basis of immune evasion by RNA virus
| Project/Area Number |
17K07296
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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 |
Structural biochemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
Ose Toyoyuki 北海道大学, 先端生命科学研究院, 准教授 (80380525)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | RNAウイルス / 結晶構造解析 / 分子間相互作用 / 相互作用解析 / 組換え調製 / 免疫不活化 / 転写 |
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| Outline of Final Research Achievements |
To evade host immunity, many pathogenic viruses inactivate host JAK-STAT pathways using diverse strategies. Measles virus utilizes P and V proteins to counteract this signaling pathway. Our data indicate that interactions between the C-terminal domain (CTD) of V and STAT2 is one order of magnitude stronger than that of the N-terminal region of V and STAT1. We also clarified those interactions are completely independent each other in solution. These results provide a novel model that MeV-V can not only inhibit the STAT2/IRF9 interaction but also disrupt pre-assembled ISGF3. For CTD of rabies virus P protein, we analyze the structures of the CTD of P of Duvenhage and of a distinct rabies virus strain to gain further insight on the nature and potential function of the hydrophobic surface. Molecular contacts suggest that the hydrophobic patch is important to intermolecular interactions with other proteins, which differ between the lyssavirus species.
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| Academic Significance and Societal Importance of the Research Achievements |
ウイルスがどの宿主・細胞に感染できるかは，細胞表面におけるウイルス蛋白質―細胞受容体の親和性だけでは説明できない。すなわち，第２因子である，宿主免疫系をかいくぐるウイルスの巧妙な策略を解明することが重要である。ここでは，免疫シグナル経路であるJAK-STAT系を構成するSTAT分子に対して，人類に対する影響が大きい麻疹ウイルス，狂犬病ウイルスが免疫系逃避のために使用している蛋白質の相互作用解析を通して，その指向性を明らかにした。精密な解離定数解析を通し，麻疹ウイルスV蛋白質はSTAT2とIRF9の相互作用を阻害するだけで無く，すでに結合状態にある両者の結合を剥がすことができることも判明した。
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Report
(4 results)
Research Products
(19 results)
