Li Wenhui, Moore Michael J, Vasilieva Natalya, Sui Jianhua, Wong Swee Kee, Berne Michael A, Somasundaran Mohan, Sullivan John L, Luzuriaga Katherine, Greenough Thomas C, Choe Hyeryun, Farzan Michael
Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics), Boston, Massachusetts 02115, USA.
Nature. 2003 Nov 27;426(6965):450-4. doi: 10.1038/nature02145.
Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.
包括导致严重急性呼吸综合征（SARS）的冠状病毒在内的冠状病毒刺突（S）蛋白，与细胞受体结合以介导其对靶细胞的感染。在此，我们从对SARS冠状病毒（SARS-CoV）敏感的Vero E6细胞中分离出一种金属肽酶——血管紧张素转换酶2（ACE2），它能有效结合SARS-CoV S蛋白的S1结构域。我们发现，可溶性形式的ACE2而非相关酶ACE1，可阻断S1结构域与Vero E6细胞的结合。用ACE2转染的293T细胞，而非用人类免疫缺陷病毒1型受体转染的细胞，可与表达S蛋白的细胞形成多核巨细胞。此外，SARS-CoV能在转染了ACE2的293T细胞上高效复制，而在未转染的细胞上则不能。最后，抗ACE2抗体而非抗ACE1抗体可阻断Vero E6细胞上的病毒复制。我们的数据共同表明，ACE2是SARS-CoV的功能性受体。
