Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63

J Gen Virol. 2012 Sep;93(Pt 9):1924-1929. doi: 10.1099/vir.0.043919-0. Epub 2012 Jun 20.


Like severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus (HCoV)-NL63 employs angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry. SARS-CoV infection causes robust downregulation of cellular ACE2 expression levels and it has been suggested that the SARS-CoV effect on ACE2 is involved in the severity of disease. We investigated whether cellular ACE2 downregulation occurs at optimal replication conditions of HCoV-NL63 infection. The expression of the homologue of ACE2, the ACE protein not used as a receptor by HCoV-NL63, was measured as a control. A specific decrease for ACE2 protein level was observed when HCoV-NL63 was cultured at 34 °C. Culturing the virus at the suboptimal temperature of 37 °C resulted in low replication of the virus and the effect on ACE2 expression was lost. We conclude that the decline of ACE2 expression is dependent on the efficiency of HCoV-NL63 replication, and that HCoV-NL63 and SARS-CoV both affect cellular ACE2 expression during infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Cell Line
  • Coronavirus Infections / enzymology*
  • Coronavirus Infections / virology*
  • Coronavirus NL63, Human / genetics
  • Coronavirus NL63, Human / physiology*
  • Down-Regulation*
  • Humans
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Virus Replication*


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2