Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry

Autor: Lin-Fa Wang, Yu-xuan Hou, Yan Li, Cheng Peng, Fang Li, Meng Yu, Zhenggang Han, Zhengli Shi
Přispěvatelé: Plazi
Rok vydání: 2010
Předmět:
Models
Molecular
Disease reservoir
Severe Acute Respiratory Syndrome Coronavirus
viruses
Severe Acute Respiratory Syndrome
medicine.disease_cause
Viral Envelope Proteins
Chiroptera
Coronaviridae
Viridae
Salt Bridge
skin and connective tissue diseases
Coronavirus
Membrane Glycoproteins
biology
biotic associations
corona viruses
virus diseases
covid
General Medicine
covid-19
Severe acute respiratory syndrome-related coronavirus
Spike Glycoprotein
Coronavirus
RNA
Viral
Receptors
Virus
Original Article
Angiotensin-Converting Enzyme 2
CETAF-taskforce
Protein Binding
Virus genetics
Molecular Sequence Data
Peptidyl-Dipeptidase A
Horseshoe bat
virus-host
pathogen-host
Viral entry
Virology
medicine
Animals
Humans
Natural reservoir
biotic relations
ACE2 Gene
Amino Acid Sequence
Rhinolophus sinicus
Disease Reservoirs
fungi
Genetic Variation
pathogens
Sequence Analysis
DNA
Virus Internalization
biotic interaction
biology.organism_classification
Protein Structure
Tertiary
Pseudotype Virus
body regions
Amino Acid Substitution
Mutagenesis
Site-Directed
Mutant Proteins
Sequence Alignment
HeLa Cells
Zdroj: Archives of Virology
ISSN: 1432-8798
0304-8608
DOI: 10.1007/s00705-010-0729-6
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1007/s00705-010-0729-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: