Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

EBioMedicine

David K. Meyerholz¹  Julia A. Klesney-Tait²  Philip H. Karp²  Andrew Thurman²  Alejandro A. Pezzulo²  Ping Tan²  Mariah R. Leidinger³  Miguel E. Ortiz⁴  Paul B. McCray, Jr.⁴  Christine Wohlford-Lenane⁴ 

[1] Corresponding authors.;Departments of Internal Medicine, University of Iowa College of Medicine, University of Iowa, Iowa City, IA, USA;Departments of Pathology, University of Iowa College of Medicine, University of Iowa, Iowa City, IA, USA;Departments of Pediatrics, University of Iowa College of Medicine, University of Iowa, Iowa City, IA, USA;

关键词: Lung;    Expression;    Alveolar type II cells;    Ciliated cells;    Immunohistochemistry;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. Materials and methods: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. Findings: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. Interpretation: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.

【 授权许可】

Unknown