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Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium.
Am J Respir Crit Care Med. 2020 07 15; 202(2):219-229.AJ

Abstract

Rationale: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to ACE2 (angiotensin-converting enzyme 2) on the airway epithelium.Objectives: The objective was to gain insight into the expression of ACE2 in the human airway epithelium.Methods: Airway epithelia sampled by fiberoptic bronchoscopy of trachea, large airway epithelia (LAE), and small airway epithelia (SAE) of nonsmokers and smokers were analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA sequencing, and 10x single-cell transcriptome analysis, with associated examination of ACE2-related microRNA.Measurements and Main Results:1) ACE2 is expressed similarly in the trachea and LAE, with lower expression in the SAE; 2) in the SAE, ACE2 is expressed in basal, intermediate, club, mucus, and ciliated cells; 3) ACE2 is upregulated in the SAE by smoking, significantly in men; 4) levels of miR-1246 expression could play a role in ACE2 upregulation in the SAE of smokers; and 5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers.Conclusions:ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection.

Authors+Show Affiliations

Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and.Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and.Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and.Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and. Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York.Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and.Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and.Department of Genetic Medicine, Weill Cornell Medical College, New York, New York; and.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32432483

Citation

Zhang, Haijun, et al. "Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium." American Journal of Respiratory and Critical Care Medicine, vol. 202, no. 2, 2020, pp. 219-229.
Zhang H, Rostami MR, Leopold PL, et al. Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium. Am J Respir Crit Care Med. 2020;202(2):219-229.
Zhang, H., Rostami, M. R., Leopold, P. L., Mezey, J. G., O'Beirne, S. L., Strulovici-Barel, Y., & Crystal, R. G. (2020). Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium. American Journal of Respiratory and Critical Care Medicine, 202(2), 219-229. https://doi.org/10.1164/rccm.202003-0541OC
Zhang H, et al. Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium. Am J Respir Crit Care Med. 2020 07 15;202(2):219-229. PubMed PMID: 32432483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium. AU - Zhang,Haijun, AU - Rostami,Mahboubeh R, AU - Leopold,Philip L, AU - Mezey,Jason G, AU - O'Beirne,Sarah L, AU - Strulovici-Barel,Yael, AU - Crystal,Ronald G, PY - 2020/5/21/pubmed PY - 2020/7/25/medline PY - 2020/5/21/entrez KW - ACE2 transcriptome KW - COVID-19 KW - coronavirus SP - 219 EP - 229 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 202 IS - 2 N2 - Rationale: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to ACE2 (angiotensin-converting enzyme 2) on the airway epithelium.Objectives: The objective was to gain insight into the expression of ACE2 in the human airway epithelium.Methods: Airway epithelia sampled by fiberoptic bronchoscopy of trachea, large airway epithelia (LAE), and small airway epithelia (SAE) of nonsmokers and smokers were analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA sequencing, and 10x single-cell transcriptome analysis, with associated examination of ACE2-related microRNA.Measurements and Main Results:1) ACE2 is expressed similarly in the trachea and LAE, with lower expression in the SAE; 2) in the SAE, ACE2 is expressed in basal, intermediate, club, mucus, and ciliated cells; 3) ACE2 is upregulated in the SAE by smoking, significantly in men; 4) levels of miR-1246 expression could play a role in ACE2 upregulation in the SAE of smokers; and 5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers.Conclusions:ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/32432483/Expression_of_the_SARS_CoV_2_ACE2_Receptor_in_the_Human_Airway_Epithelium_ DB - PRIME DP - Unbound Medicine ER -