A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.
A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.
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DOI：
10.1038/nm1267
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发表时间：
2005-08
期刊：
影响因子：
82.9
通讯作者：
Penninger JM
中科院分区：
文献类型：
--
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
在2003年的几个月里，一种新发现的名为严重急性呼吸综合征(SARS)的疾病在世界各地迅速传播。一种新的冠状病毒(SARS-CoV)被确定为SARS的病原体，它引发了严重的肺炎和急性的、通常是致命的肺衰竭。此外，在受感染的人中，西班牙流感等流感和新的呼吸道疾病病毒的出现导致了急性肺衰竭造成的高致死率。在细胞系中，血管紧张素转换酶2(ACE2)被认为是一种潜在的SARS-CoV受体。SARS冠状病毒感染的高致命性、其巨大的经济和社会影响、对新爆发的恐惧以及此类病毒可能被误用为生物武器，使得了解SARS冠状病毒的发病机制变得至关重要。在这里，我们提供了第一个遗传学证据，证明ACE2是体内一个重要的SARS-CoV受体。SARS冠状病毒感染和SARS冠状病毒的刺突蛋白降低了ACE2的表达。值得注意的是，向小鼠体内注射SARS-CoV Spike会加重体内的急性肺衰竭，这种情况可以通过阻断肾素-血管紧张素途径来缓解。这些结果提供了SARS冠状病毒感染导致严重且往往致命的肺衰竭的分子解释，并为SARS和可能的其他呼吸道疾病病毒提供了一种合理的治疗方法。本文的在线版本(doi：10.1038/nm1267)包含补充材料，授权用户可以使用。
During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
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
通讯作者：
Farzan M
影响因子：
64.8
作者：
Crackower, MA;Sarao, R;Penninger, JM
通讯作者：
Penninger, JM
影响因子：
3.3
作者：
Imai, Y;Nakagawa, S;Miyasaka, K
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Miyasaka, K
影响因子：
20.1
作者：
Donoghue, M;Hsieh, F;Acton, S
通讯作者：
Acton, S
DOI：
10.1016/j.bbrc.2004.08.208
发表时间：
2004-10-22
影响因子：
3.1
作者：
Itoyama, S;Keicho, N;Sasazuki, T
通讯作者：
Sasazuki, T