| Project/Area Number |
25293111
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
SHIMIZU HIROYUKI 国立感染症研究所, その他部局等, その他 (90270644)
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| Co-Investigator(Renkei-kenkyūsha) |
NISHIMURA YORIHIRO 国立感染症研究所, ウイルス第二部第二室, 主任研究官 (00392316)
KATAOKA CHIKAKO 北海道大学, 人獣共通感染症リサーチセンター, 特任助教 (10646623)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | エンテロウイルス / エンテロウイルス71 / 受容体 / PSGL-1 / 手足口病 / レセプター / 動物モデル / 病原性 / 感染モデル / 分子進化 / カニクイザル |
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| Outline of Final Research Achievements |
In this research project, we investigated the involvement of the capsid amino acid mutation of enterovirus 71 (EV 71) in the viral phenotype and pathogenicity. Specific capsid amino acid residues including VP1-145 around the 5-fold vertex of the EV71 capsid were responsible for various viral phenotypes such as PSGL-1-binding specificity and neutralization antigenicity. In a cynomolgus monkey model, we demonstrated potent in vivo selection of EV71 variants with VP1-145E in host adaptation and the resultant VP1-145E variants were mainly associated with the development of viremia and neuropathogenesis presumably in a PSGL-1 independent manner. Therefore, the results suggest the in vivo involvement of amino acid polymorphisms at VP1-145 in cell-specific viral replication, in vivo fitness, and pathogenesis in EV71-infected individuals.
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