SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

Biology Biology
Cell Atlas Cell Atlas
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Statistics Statistics
Ben Mead Ben Mead
Benjamin Doran Benjamin Doran
Carly Ziegler Carly Ziegler
Constantine Tzouanas Constantine Tzouanas
James Gatter James Gatter
Marc Wadsworth II Marc Wadsworth II
Marko Vukovic Marko Vukovic
Sam Allon Sam Allon
Sarah Nyquist Sarah Nyquist
Vincent Miao Vincent Miao

Ziegler et al.▾ Ziegler, C.G.K.*, Allon, S.J.*, Nyquist, S.K.*, Mbano, I.M.*, Miao, V.N., Tzouanas, C.N., Cao, Y., Yousif, A.S., Bals, J., Hauser, B.M., Feldman, J., Muus, C., Wadsworth II, M.H., Kazer, S.W., Hughes, T.K., Doran, B., Gatter, G.J., Vukovic, M., Taliaferro, F., Mead, B.E., Guo, Z., Wang, J.P., Gras, D., Plaisant, M., Ansari, M., Angelidis, I., Adler, H., Sucre, J.M.S., Taylor, C.J., Lin, B., Waghray, A., Mitsialis, V., Dwyer, D.F., Buchheit, K.M., Boyce, J.A., Barrett, N.A., Laidlaw, T.M., Carroll, S.L., Colonna, L., Tkachev, V., Peterson, C.W., Yu, A., Zheng, H.B., Gideon, H.P., Winchell, C.G., Lin, P.L., Bingle, C.D., Snapper, S.B., Kropski, J.A., Theis, F.J., Schiller, H.B., Zaragosi, L.-E., Barbry, P., Leslie, A., Kiem, H.-P., Flynn, J.L., Fortune, S.M., Berger, B., Finberg, R.W., Kean, L.S., Garber, M., Schmidt, A.G., Lingwood, D., Shalek, A.K.#, Ordovas-Montanes, J.#, HCA Lung Biological Network

Cell , Volume 181

April, 2020

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.