Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor

Biochem Biophys Res Commun. 2004 Jul 9;319(4):1216-21. doi: 10.1016/j.bbrc.2004.05.114.

Abstract

The angiotensin converting enzyme 2 (ACE2) has been identified as a receptor for the severe acute respiratory syndrome associated coronavirus (SARS-CoV). Here we show that ACE2 expression on cell lines correlates with susceptibility to SARS-CoV S-driven infection, suggesting that ACE2 is a major receptor for SARS-CoV. The soluble ectodomain of ACE2 specifically abrogated S-mediated infection and might therefore be exploited for the generation of inhibitors. Deletion of a major portion of the cytoplasmic domain of ACE2 had no effect on S-driven infection, indicating that this domain is not important for receptor function. Our results point to a central role of ACE2 in SARS-CoV infection and suggest a minor contribution of the cytoplasmic domain to receptor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism*
  • Carboxypeptidases / chemistry
  • Carboxypeptidases / genetics
  • Carboxypeptidases / metabolism*
  • Cell Line
  • Disease Susceptibility
  • Humans
  • Mutation
  • Peptidyl-Dipeptidase A
  • Protein Structure, Tertiary
  • Receptors, Virus / metabolism*
  • Sequence Alignment
  • Severe Acute Respiratory Syndrome / metabolism*
  • Severe acute respiratory syndrome-related coronavirus / metabolism*
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity
  • Solubility
  • Viral Proteins / metabolism*

Substances

  • Antiviral Agents
  • Receptors, Virus
  • Viral Proteins
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2