SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
复制标题
DOI：
10.1016/j.cell.2020.04.035
复制
发表时间：
2020-05-28
期刊：
影响因子：
64.5
通讯作者：
Ordovas-Montanes, Jose
中科院分区：
文献类型：
--
作者：
Ziegler, Carly G. K.;Allon, Samuel J.;Ordovas-Montanes, Jose
了解导致COVID-19的严重急性呼吸综合征冠状病毒分支2 （SARS-CoV-2）的发病机制迫在眉睫。SARS-CoV-2刺突(S)蛋白结合血管紧张素转换酶2 (ACE2)，并与宿主蛋白酶（主要是跨膜丝氨酸蛋白酶2 (TMPRSS2)）协同作用，促进细胞进入。SARS-CoV-2在宿主组织中靶向的细胞亚群以及调节ACE2表达的因子尚不清楚。在这里，我们利用人类、非人类灵长类动物和小鼠健康和疾病的单细胞rna测序（scRNA-seq）数据集，在组织驻留细胞亚群中发现SARS-CoV-2的假定靶点。我们在肺II型肺细胞、回肠吸收性肠细胞和鼻杯分泌细胞中发现了ACE2和TMPRSS2共表达细胞。引人注目的是，我们在体外使用气道上皮细胞发现ACE2是人类干扰素刺激基因（ISG），并将我们的发现扩展到体内病毒感染。我们的数据表明，SARS-CoV-2可能利用物种特异性干扰素驱动的ACE2上调来增强感染，ACE2是肺损伤期间的一种组织保护介质。
There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.