Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium

• Published in: American journal of respiratory and critical care medicine 2020-07, Vol.202 (2), p.219-229
• Main Authors: Zhang, Haijun, Rostami, Mahboubeh R, Leopold, Philip L, Mezey, Jason G, O'Beirne, Sarah L, Strulovici-Barel, Yael, Crystal, Ronald G
• Format: Article
• Language: English
• Subjects: Angiotensin-Converting Enzyme 2; Betacoronavirus; Case-Control Studies; Coronavirus Infections - metabolism; COVID-19; Female; Gene expression; Genetics; Humans; Lung - metabolism; Lung diseases; Male; Original; Pandemics; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - metabolism; Respiratory Mucosa - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Sex Factors; Smoking - metabolism; Trachea - metabolism
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.202003-0541oc

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 (angiotensin-converting enzyme 2) on the airway epithelium. The objective was to gain insight into the expression of in the human airway epithelium. 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 and other coronavirus infection-related genes using microarray, RNA sequencing, and 10x single-cell transcriptome analysis, with associated examination of -related microRNA. ) is expressed similarly in the trachea and LAE, with lower expression in the SAE; ) in the SAE, is expressed in basal, intermediate, club, mucus, and ciliated cells; ) is upregulated in the SAE by smoking, significantly in men; ) levels of miR-1246 expression could play a role in upregulation in the SAE of smokers; and ) is expressed in airway epithelium differentiated 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. , 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.