Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract

Smith, J.C., Sausville, E. L., Girish, V., Yuan, M.L., Vasudevan, A., John, K.M., Sheltzer, J. M. (May 2020) Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract. Dev Cell, 53 (5). 514-529.e3. ISSN 1534-5807

URL: https://pubmed.ncbi.nlm.nih.gov/32425701/
DOI: 10.1016/j.devcel.2020.05.012

Abstract

The factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of secretory cells in the respiratory tract. Chronic smoke exposure triggers the expansion of this cell population and a concomitant increase in ACE2 expression. In contrast, quitting smoking decreases the abundance of these secretory cells and reduces ACE2 levels. Finally, we demonstrate that ACE2 expression is responsive to inflammatory signaling and can be upregulated by viral infections or interferon treatment. Taken together, these results may partially explain why smokers are particularly susceptible to severe SARS-CoV-2 infections. Furthermore, our work identifies ACE2 as an interferon-stimulated gene in lung cells, suggesting that SARS-CoV-2 infections could create positive-feedback loops that increase ACE2 levels and facilitate viral dissemination.

Item Type: Paper
CSHL Authors:
Communities: CSHL labs > Sheltzer lab
Depositing User: Adrian Gomez
Date: 16 May 2020
Date Deposited: 21 May 2020 17:06
Last Modified: 06 Jul 2020 14:54
PMCID: PMC7229915
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39471

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving