SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
By Carly G. K. Ziegler, Samuel J. Allon, Sarah K Nyquist, Ian M Mbano, Vincent N Miao, C. Tzouanas, Yuming Cao, A. Yousif, Julia Bals, B. Hauser and 106 more. Cell, 2020
2,159 citations recorded by the source corpus.
Summary 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.
Subfields: Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/4ee62ec5efcd18347b76bbb77f979199b7c2b8e4
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Citations in the corpus
- The protein expression profile of ACE2 in human tissues (2020, neutral): “…number of cells in respiratory epithelia susceptible for SARS-CoV-2 infection, which could potentially explain the possibility of SARS-CoV-2 to enter via ACE2 receptors in the respiratory tract despite low ACE2 expression under normal conditions (preprint: Chua et al , 2020; Ziegler et al , 2020).”
- Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, neutral): “These cells are probably ‘ground-zero’ for early infection and subsequent replication due to their expression of ACE2 [25].”
- COVID-19 and the human innate immune system (2021, background): “In the lung, ACE2 and TMPRSS2 expression has been mainly identified in alveolar epithelial type II cells (Qi et al., 2020; Zou et al., 2020).”