SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ziegler, CGK; Allon, SJ; Nyquist, SK; Mbano, IM; Miao, VN; Tzouanas, CN; Cao, Y; Yousif, AS; Bals, J; Hauser, BM; Feldman, J; Muus, C; Wadsworth, MH; Kazer, SW; Hughes, TK; Doran, B; Gatter, GJ; Vukovic, M; Taliaferro, F; Mead, BE; Guo, Z; Wang, JP; Gras, D; Plaisant, M; Ansari, M; Angelidis, I; Adler, H; Sucre, JMS; Taylor, CJ; Lin, B; Waghray, A; Mitsialis, V; Dwyer, DF; Buchheit, KM; Boyce, JA; Barrett, NA; Laidlaw, TM; Carroll, SL; Colonna, L; Tkachev, V; Peterson, CW; Yu, A; Zheng, HB; Gideon, HP; Winchell, CG; Lin, PL; Bingle, CD; Snapper, SB; Kropski, JA; Theis, FJ; Schiller, HB; Zaragosi, L-E; Barbry, P; Leslie, A; Kiem, H-P; Flynn, JL; Fortune, SM; Berger, B; Finberg, RW; Kean, LS; Garber, M; Schmidt, AG; Lingwood, D; Shalek, AK; Ordovas-Montanes, J; HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org, ; HCA Lung Biological Network,

Published Date

  • May 28, 2020

Published In

Volume / Issue

  • 181 / 5

Start / End Page

  • 1016 - 1035.e19

PubMed ID

  • 32413319

Pubmed Central ID

  • 32413319

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2020.04.035

Language

  • eng

Conference Location

  • United States