| Project/Area Number |
15K19118
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Shiota Tomoyuki 国立感染症研究所, ウイルス第二部, リサーチ・レジデント (80616144)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | hepatitis E virus (HEV) / non-enveloped HEV / receptor candidate / E型肝炎ウイルス（HEV） / レセプター（ウイルス受容体） / 膜タンパク質 / HEV感受・非感受性細胞 / 機能獲得・損失実験 / non-envelope形態 / 細胞外領域欠損変異体 / 共免疫沈降 / ウイルス様中空粒子（VLP） / HEV非感受性細胞 / non-envelope HEV / 感染阻害 / ゲノム編集 / 感受性復帰 / CRIPR/Cas9 / Fc融合タンパク質 / 免疫沈降法 / 結合・感染阻害 / CRISPR/Cas9 |
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| Outline of Final Research Achievements |
Hepatitis E virus (HEV) causes acute and fulminant hepatitis worldwide. Although enveloped (e) and non-enveloped (ne) forms of HEV have been discovered, host factors involved in infection, including receptors, remain to be elucidated. Here, we identified a promising receptor candidate as an essential host factor for HEV infection. The candidate expression was lower in four HEV-non-permissive cell subclones than in an HEV-permissive subclone. The candidate knockout cells lost HEV permissibility, suggesting that the candidate is critical for HEV infection. Stable expression of the candidate in an HEV-non-permissive subclone provided permissibility only to infection by neHEV; expression of the candidate lacking the ectodomain did not. Direct interaction between neHEV and the the candidate ectodomain was confirmed by co-precipitation using a soluble candidate-Fc. These results strongly suggest that the candidate is a key molecule for cellular attachment and entry of neHEV.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、食品媒介性の感染が増加する一方で有効な対策法が存在しないE型肝炎ウイルス（HEV）について、HEVに対する感受・非感受性細胞の解析からレセプター（ウイルス受容体）候補を同定することに成功した。現在までにHEV感染規定レセプターは同定されていないが、HEVのトロピズム（生体内指向性）を明らかにする為にもその同定は必要不可欠である。HEVは肝細胞外感染も近年多数報告され、経口感染経路の解明や肝細胞での急性・劇症症状、更には妊婦における高い致死率などの解明に端緒を与える可能性があり、学術的意義は極めて高い。また、レセプターを基軸としたワクチンや治療薬の開発による社会的意義も大きい。
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