Intersubject Variation in ACE2 Protein Expression in Human Airway Epithelia and Its Relationship to Severe Acute Respiratory Syndrome Coronavirus 2

J Infect Dis. 2021 Oct 28;224(8):1357-1361. doi: 10.1093/infdis/jiab383.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) initiates entry into airway epithelia by binding its receptor, angiotensin-converting enzyme 2 (ACE2).

Methods: To explore whether interindividual variation in ACE2 abundance contributes to variability in coronavirus disease 2019 (COVID-19) outcomes, we measured ACE2 protein abundance in primary airway epithelial cultures derived from 58 human donor lungs.

Results: We found no evidence for sex- or age-dependent differences in ACE2 protein expression. Furthermore, we found that variations in ACE2 abundance had minimal effects on viral replication and induction of the interferon response in airway epithelia infected with SARS-CoV-2.

Conclusions: Our results highlight the relative importance of additional host factors, beyond viral receptor expression, in determining COVID-19 lung disease outcomes.

Keywords: ACE2; COVID-19; SARS-CoV-2; airway epithelia; risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / analysis
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Biological Variation, Population
  • Bronchi / cytology
  • Bronchi / pathology
  • Bronchi / virology
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Epithelial Cells
  • Female
  • Humans
  • Male
  • Primary Cell Culture
  • Receptors, Coronavirus / analysis
  • Receptors, Coronavirus / metabolism*
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / virology
  • SARS-CoV-2 / metabolism*
  • Sex Factors
  • Virus Internalization

Substances

  • Receptors, Coronavirus
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2