2011-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/696507摘要：嚴重急性呼吸道症候群(SARS)是由SARS 相關冠狀病毒(SARS-CoV)所引起之一非典型肺炎，其致死率接近百分之十。SARS-CoV 是在2003 年SARS 爆發時所鑑定出，由基因序列比對推測是從感染雪貂及蝙蝠相關冠狀病毒所演化而來。雖然目前SARS-CoV 的感染已受控制，但感染野生動物的SARS-CoV 相關病毒則不易控制及監測。同時，SARS-CoV 感染所造成之急性呼吸道痛苦症候群、肺纖維化，甚至造成呼吸衰竭之分子機制仍未完全明瞭。ACE2 是SARS-CoV 的功能性受體，但亦可能存在著參與SARS-CoV 感染尚未被瞭解的組織特異性病毒受體或共同受體。我們最近的研究顯示SARS-CoV spike 蛋白質與ACE2 受體結合所引發之訊息傳遞可正調控下游基因CCL-2 之表現，此結果可能與SARS-CoV 感染導致肺纖維化之致病相關。本計畫擬利用重組之SARS-CoV spike 蛋白質或SARS-CoV 類病毒顆粒瞭解SARS-CoV spike 蛋白質與ACE2 受體結合所引發之訊息傳遞及可能造成ACE2 受體由細胞表面脫離之分子機制。同時，擬利用細胞培養及動物模式系統探討宿主細胞因子如ACE2 受體及vimentin 參與病毒早期感染及致病之作用機轉。<br> Abstract: Severe acute respiratory syndrome (SARS) is an atypical pneumonia caused bySARS-associated coronavirus (SARS-CoV) that was identified from an outbreak in 2003. Itsmortality rate is close to 10%. SARS-CoV was evolved from SARS-related coronavirus ofcivet cats and bats. Although SARS-CoV infection is under control, wild animals carriedSARS-related coronaviruses are not easy to be governed and monitored. In addition,molecular mechanisms of SARS-CoV pathogenesis including acute respiratory distresssyndrome (ARDS), fibrosis, and respiratory failure are not fully understood.Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV. However,there are possibilities that other virus receptors or co-receptors are involved to mediate thetissue tropism of SARS-CoV infection. Recently, our studies indicated thatSARS-CoV-associated lung fibrosis may be resulted from an up-regulation of the chemokine(C-C motif) ligand 2 (CCL-2) through a SARS-CoV spike-ACE2 signaling pathway. In thisstudy, the viral spike protein and non-infectious SARS-CoV-like particles (VLPs) containingthe viral spike, E, and M proteins would be applied to elucidate the mechanisms of thespike-mediated ACE2 signaling involved in ACE2 shedding and to examine the roles of hostfactors such as ACE2 and vimentin involved in the cell entry and pathogenesis ofSARS-CoV in both culture cells and animal models.嚴重急性呼吸道症候群冠狀病毒病毒感染受器細胞因子SARS-CoVvirus infectionreceptorcellular factor