Project/Area Number |
17K19563
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
Pathology, Infection/Immunology, and related fields
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Research Institution | Kyushu University |
Principal Investigator |
Yanagi Yusuke 九州大学, 医学研究院, 教授 (40182365)
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Research Collaborator |
Hashiguchi takao
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Project Period (FY) |
2017-06-30 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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Keywords | ムンプスウイルス / 膜融合 / ウィルス / 微生物 / 感染症 |
Outline of Final Research Achievements |
Mumps virus (MuV) is an enveloped negative-stranded RNA virus in the family Paramyxoviridae. Two viral envelope glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion (F) protein, mediate membrane fusion. The MuV F protein (MuV-F) is initially synthesized as an inactive precursor F0, and then activated by the host cell protease furin which cleaves F0 into heterodimers F1 and F2. Efficient membrane fusion and MuV-F processing were observed in HEK293 and Vero cells, but not in the cell line X and furin-deficient LoVo cells, upon expression of the HN and F proteins. Co-transfection of the furin-expressing plasmid restored membrane fusion in LoVo cells, but not in the cell line X, indicating that furin alone is not sufficient for the cleavage of MuV-F. By the cDNA library screening, we identified the proteins that confer on the cell line X the ability to cleave MuV-F and cause membrane fusion. These proteins may play an important role in the MuV-F processing.
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Academic Significance and Societal Importance of the Research Achievements |
流行性耳下腺炎(おたふくかぜ、ムンプス)の原因であるムンプスウイルスは、唾液腺炎以外に精巣炎、卵巣炎、乳腺炎、膵炎、髄膜炎、脳炎、難聴などを起こす。予防のための生ワクチンが存在するが、副反応が起こることがあるため、わが国では任意接種になっている。そのため、ワクチン接種率は低く、毎年数十万人の患者が出ている。特異的な治療薬はない。本研究では、ムンプスウイルスが標的細胞に感染する際に必要な細胞側の蛋白質を同定した。この蛋白質の働きを詳細に解析することにより、ムンプスウイルスの細胞感染メカニズムが明らかになるだけでなく、抗ウイルス薬開発につながる可能性がある。
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