| Project/Area Number |
19790346
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
MATSUYAMA Shutoku National Institute of Infectious Diseases, ウイルス第三部第四室, 室長 (90373399)
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| Project Period (FY) |
2007 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥510,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | S蛋白 / エンベロープ / 構造変化中間体 / 感染 / 膜融合 / ウイルス / MHV / TMPRSS2 / 細胞侵入 / プロテアーゼ / 肺炎 / 組織指向性 / ウイルス感染 / 構造変化 / 中間体 |
|---|
| Research Abstract |
Previous studies have demonstrated that the SARS-CoV S protein requires proteolytic cleavage by elastase, cathepsin or TMPRSS2 for S-mediated cell-cell or virus-cell membrane fusion. Activation of viral glycoprotein (GP) by protease also has been reported for influenza virus. The most distinctive difference between influenza virus and SARS-CoV is the stage during virus replication in which viral glycoproteins are cleaved by proteases. In influenza virus, the protease makes a simple cut in the GP during maturation. In contrast, SARS-CoV S protein is cleaved by the protease following receptor-induced conformational changes. The protease cleavage site in S protein is thought to be exposed only after receptor binding. In support of this model, we reported that the S protein of mouse hepatitis virus type 2 (MHV-2), which is highly similar to the S protein of SARS-CoV, requires two-step conformational changes mediated by sequential receptor binding and proteolysis to be activated for membrane fusion. Such a mechanism allows for tight temporal control over fusion by protecting the activating cleavage site from premature proteolysis yet allowing efficient cleavage upon binding to the receptor on target cells.
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