Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract.
Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract.
复制标题
DOI：
10.1016/j.ebiom.2020.102976
复制
发表时间：
2020-10
期刊：
影响因子：
11.1
通讯作者：
Meyerholz DK
中科院分区：
文献类型：
--
作者：
Ortiz ME;Thurman A;Pezzulo AA;Leidinger MR;Klesney-Tait JA;Karp PH;Tan P;Wohlford-Lenane C;McCray PB Jr;Meyerholz DK
自2002年以来，人畜传播的冠状病毒导致了三次疾病暴发，包括目前由SARS-CoV-2引起的新冠肺炎大流行。它的有效传播和疾病严重程度的范围引发了关于病毒-受体相互作用的贡献的问题。ACE2是一种宿主外肽酶，也是SARS-CoV-2的受体。许多报告描述了ACE2的mRNA丰度和组织分布；然而，信使核糖核酸丰度并不总是代表蛋白质水平。目前，评估ACE2蛋白及其与其他SARS-CoV-2易感因子的相关性的数据有限。我们利用单细胞核糖核酸测序和免疫组织化学方法系统地检测了人的上呼吸道和下呼吸道，以确定受体的表达，并评估其与严重新冠肺炎危险因素的关系。我们的结果显示，ACE2蛋白在鼻腔和肺泡区域最高，这两个区域分别是假定的病毒传播和严重疾病发生的部位。在肺实质中，ACE2蛋白位于肺泡II型细胞的一小部分顶面，并与SARS-CoV2进入的辅助因子TMPRSS2共定位。重症新冠肺炎的肺部危险因素不增加血管紧张素转换酶2蛋白表达。此外，血管紧张素转换酶2蛋白在儿童中没有减少，这是严重新冠肺炎发生率较低的人群。这些结果为血管紧张素转换酶2蛋白在呼吸道中的定位及其与新冠肺炎易感因素的关系提供了新的见解。
Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.
登录
查看更多内容
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：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
64.8
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
通讯作者：
Penninger JM
DOI：
10.1074/jbc.m505111200
发表时间：
2005-08-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lambert DW;Yarski M;Warner FJ;Thornhill P;Parkin ET;Smith AI;Hooper NM;Turner AJ
通讯作者：
Turner AJ
影响因子：
6.1
作者：
Liu Wei;Tao Zhao-Wu;Hu Yi
通讯作者：
Hu Yi