Rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in Chinese macaques.
Rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in Chinese macaques.
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DOI：
10.1016/j.virol.2008.08.016
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发表时间：
2008-11-10
期刊：
影响因子：
3.7
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Chen Y;Liu L;Wei Q;Zhu H;Jiang H;Tu X;Qin C;Chen Z
血管紧张素转换酶 2 (ACE2) 是严重急性呼吸综合征冠状病毒 (SARS-CoV) 用于进入靶细胞的受体，因此在 SARS 发病机制中发挥着重要作用。由于中国恒河猴 (rh) 猕猴在感染 SARS-CoV 后通常不会发展为 SARS，因此有人认为 rh-ACE2 可能无法有效支持病毒进入。为了确定 rh-ACE2 在体内早期肺部发病机制中的作用，我们研究了 11 只实验感染致病性 SARS-CoVPUMC01 菌株的中国恒河猴。通过逆转录聚合酶链式反应从所有动物中扩增 Rh-ACE2 基因，并使用假病毒进入试验在体外研究其功能。在 rh-ACE2 基因中发现了许多自然的非同义 (NS) 变化。与人类 (hu) ACE2 相比，rh-ACE2 中发现了 38 个一致的 NS 变化。由于这些变化不与 SARS-CoV 的受体结合域相互作用，因此 rh-ACE2 在支持病毒进入方面通常与人类同源物一样有效。然而，Rh-ACE2 比 hu-ACE2 更具多态性。克隆 Rh11-7 中额外的零星 NS 取代降低了 rh-ACE2 蛋白表达水平，并且不能有效支持病毒进入。进一步的诱变分析表明，自然突变 Y217N 显着改变 ACE2 表达和进入效率。此外，将Y217N突变引入hu-ACE2会导致表达下调并降低病毒进入效率。这些结果表明 Y217N 突变在调节 SARS-CoV 感染中发挥作用。我们的结果为了解 rh-ACE2 在非人灵长类动物模型中 SARS 肺部发病机制中的作用提供了见解。
Angiotensin converting enzyme 2 (ACE2) is the receptor that severe acute respiratory syndrome coronavirus (SARS-CoV) utilizes for target cell entry and, therefore, plays an important role in SARS pathogenesis. Since Chinese rhesus (rh) macaques do not usually develop SARS after SARS-CoV infection, it has been suggested that rh-ACE2 probably does not support viral entry efficiently. To determine the role of rh-ACE2 in early lung pathogenesis in vivo, we studied eleven Chinese rhesus monkeys experimentally infected with a pathogenic SARS-CoVPUMC01 strain. Rh-ACE2 genes were amplified from all animals by reverse transcription polymerase chain reaction, and their function was studied in vitro using a pseudovirus entry assay. Many natural non-synonymous (NS) changes were found in rh-ACE2 genes. Compared to human (hu) ACE2, thirty-eight consensus NS changes were found in rh-ACE2. Since these changes do not interact with the receptor binding domain of SARS-CoV, rh-ACE2 in general is as effective as human homolog in supporting viral entry. Rh-ACE2, however, is more polymorphic than hu-ACE2. Additional sporadic NS substitutions in clone Rh11-7 reduced the level of rh-ACE2 protein expression and did not support viral entry effectively. Further mutagenesis analysis showed that a natural mutation Y217N dramatically alters ACE2 expression and entry efficiency. Moreover, introduction of the Y217N mutation into hu-ACE2 caused the down-regulation of expression and reduced viral entry efficiency. These results indicate that the Y217N mutation plays a role in modulating SARS-CoV infection. Our results provide insights for understanding the role of rh-ACE2 in SARS lung pathogenesis in a non-human primate model.
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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：
30.8
作者：
Chan VS;Chan KY;Chen Y;Poon LL;Cheung AN;Zheng B;Chan KH;Mak W;Ngan HY;Xu X;Screaton G;Tam PK;Austyn JM;Chan LC;Yip SP;Peiris M;Khoo US;Lin CL
通讯作者：
Lin CL
DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang IC;Bosch BJ;Li F;Li W;Lee KH;Ghiran S;Vasilieva N;Dermody TS;Harrison SC;Dormitzer PR;Farzan M;Rottier PJ;Choe H
通讯作者：
Choe H
DOI：
10.1016/s0140-6736(03)13967-0
发表时间：
2003-07-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Kuiken T;Fouchier RA;Schutten M;Rimmelzwaan GF;van Amerongen G;van Riel D;Laman JD;de Jong T;van Doornum G;Lim W;Ling AE;Chan PK;Tam JS;Zambon MC;Gopal R;Drosten C;van der Werf S;Escriou N;Manuguerra JC;Stöhr K;Peiris JS;Osterhaus AD
通讯作者：
Osterhaus AD
影响因子：
11.4
作者：
Li, WH;Zhang, CS;Sui, JH;Kuhn, JH;Moore, MJ;Luo, SW;Wong, SK;Huang, IC;Xu, KM;Vasilieva, N;Murakami, A;He, YQ;Marasco, WA;Guan, Y;Choe, HY;Farzan, M
通讯作者：
Farzan, M