美国哈佛医学院Jose Ordovas-Montanes、麻省理工学院Alex K. Shalek等研究人员合作发现，新冠病毒（SARS-CoV-2）受体ACE2是人气道上皮细胞中的干扰素刺激基因，并在组织中特定的细胞亚群中检测到。2020年4月24日，《细胞》在线发表了这一成果。
研究人员利用人类、非人灵长类动物以及小鼠单细胞RNA测序（scRNA-seq）的健康与疾病数据集，来揭示了组织驻留细胞亚群中SARS-CoV-2的潜在靶标。研究人员确定ACE2和TMPRSS2共表达细胞在肺II型肺细胞、回肠吸收性肠上皮细胞和鼻腔中分泌粘液的杯状细胞。
令人惊讶的是，研究人员利用体外气道上皮细胞发现ACE2是受人干扰素刺激的基因（ISG），并将这些发现拓展到体内病毒感染。这些数据表明SARS-CoV-2可以利用物种特异性干扰素驱动的ACE2上调来增强感染，而ACE2原本是肺损伤时的一种组织保护介导因子。
据了解，目前迫切需要了解新冠病毒（SARS-CoV-2）导致严重急性呼吸系统综合症（COVID-19）的发病机理。SARS-CoV-2突刺（S）蛋白与ACE2结合，并与宿主蛋白酶（主要为TMPRSS2）协同作用，促进细胞进入。宿主组织中SARS-CoV-2靶向的细胞亚群以及调节ACE2表达的因子仍然未知。
附：英文原文
Title: SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues
Author: Carly G.K. Ziegler, Samuel J. Allon, Sarah K. Nyquist, Ian M. Mbano, Vincent N. Miao, Constantine N. Tzouanas, Yuming Cao, Ashraf S. Yousif, Julia Bals, Blake M. Hauser, Jared Feldman, Christoph Muus, Marc H. Wadsworth, Samuel W. Kazer, Travis K. Hughes, Benjamin Doran, G. James Gatter, Marko Vukovic, Faith Taliaferro, Benjamin E. Mead, Zhiru Guo, Jennifer P. Wang, Delphine Gras, Magali Plaisant, Meshal Ansari, Ilias Angelidis, Heiko Adler, Jennifer M.S. Sucre, Chase J. Taylor, Brian Lin, Avinash Waghray, Vanessa Mitsialis, Daniel F. Dwyer, Kathleen M. Buchheit, Joshua A. Boyce, Nora A. Barrett, Tanya M. Laidlaw, Shaina L. Carroll, Lucrezia Colonna, Victor Tkachev, Christopher W. Peterson, Alison Yu, Hengqi Betty Zheng, Hannah P. Gideon, Caylin G. Winchell
Issue&Volume: 2020-04-24
Abstract: 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 ACE2, and in concert with host proteases, principally 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 amongst 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 discover 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.
DOI: 10.1016/j.cell.2020.04.035
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30500-6