Angiotensin-converting Enzyme 2 (ACE2) Proteins of Different Bat Species Confer Variable Susceptibility to SARS-CoV Entry

Arch Virol. 2010 Oct;155(10):1563-9. doi: 10.1007/s00705-010-0729-6. Epub 2010 Jun 22.

Abstract

The discovery of SARS-like coronavirus in bats suggests that bats could be the natural reservoir of SARS-CoV. However, previous studies indicated the angiotensin-converting enzyme 2 (ACE2) protein, a known SARS-CoV receptor, from a horseshoe bat was unable to act as a functional receptor for SARS-CoV. Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. The results show that ACE2s of Myotis daubentoni and Rhinolophus sinicus support viral entry mediated by the SARS-CoV S protein, albeit with different efficiency in comparison to that of the human ACE2. Further, the alteration of several key residues either decreased or enhanced bat ACE2 receptor efficiency, as predicted from a structural modeling study of the different bat ACE2 molecules. These data suggest that M. daubentoni and R. sinicus are likely to be susceptible to SARS-CoV and may be candidates as the natural host of the SARS-CoV progenitor viruses. Furthermore, our current study also demonstrates that the genetic diversity of ACE2 among bats is greater than that observed among known SARS-CoV susceptible mammals, highlighting the possibility that there are many more uncharacterized bat species that can act as a reservoir of SARS-CoV or its progenitor viruses. This calls for continuation and expansion of field surveillance studies among different bat populations to eventually identify the true natural reservoir of SARS-CoV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Chiroptera
  • Disease Reservoirs
  • Genetic Variation
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Peptidyl-Dipeptidase A / physiology*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Viral / genetics
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Receptors, Virus / physiology*
  • SARS Virus / physiology*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / metabolism
  • Virus Internalization*

Substances

  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • Mutant Proteins
  • RNA, Viral
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2

Associated data

  • GENBANK/GQ999931
  • GENBANK/GQ999932
  • GENBANK/GQ999933
  • GENBANK/GQ999934
  • GENBANK/GQ999935
  • GENBANK/GQ999936
  • GENBANK/GQ999937
  • GENBANK/GQ999938