Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
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DOI:
10.1038/nature02145
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发表时间:
2003-11-27
期刊:
影响因子:
64.8
通讯作者:
Farzan M
Farzan M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M

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冠状病毒的尖峰蛋白,包括导致严重急性呼吸综合征(SARS)的冠状病毒,与细胞受体辅助介导其靶细胞的感染。在这里,我们确定了从SARS冠状病毒(SARS-COV)渗透性E6细胞分离的金属肽酶,血管紧张素转化酶2(ACE2),可有效地结合SARS-COV S蛋白的S1域。我们发现,ACE2的可溶形式,而不是相关酶ACE1的可溶性形式,S1结构域与VERO E6细胞的关联阻断了。用ACE2转染的293T细胞,而不是用人免疫缺陷病毒-1受体转染的细胞,它们用表达S蛋白的细胞形成多核合成曲霉。此外,SARS-COV在ACE2转染但未被模拟转染的293T细胞上有效复制。最后,抗ACE2而不是抗ACE1抗体阻止了VERO E6细胞上的病毒复制。我们的数据一起表明ACE2是SARS-COV的功能受体。 本文的在线版本(doi:10.1038/nature02145)包含补充材料,可供授权用户使用。
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. The online version of this article (doi:10.1038/nature02145) contains supplementary material, which is available to authorized users.
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发表时间: 1992-06-04
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影响因子: 64.8
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