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

Identifieur interne : 002156 ( Ncbi/Curation ); précédent : 002155; suivant : 002157

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

Auteurs : Yuxuan Hou ; Cheng Peng ; Meng Yu ; Yan Li ; Zhenggang Han ; Fang Li [États-Unis] ; Lin-Fa Wang ; Zhengli Shi

Source :

RBID : PMC:7086629

Descripteurs français

English descriptors

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.

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.


Url:
DOI: 10.1007/s00705-010-0729-6
PubMed: 20567988
PubMed Central: 7086629

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PMC:7086629

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Yuxuan Hou
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<term>Disease Reservoirs</term>
<term>Genetic Variation</term>
<term>HeLa Cells</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Mutagenesis, Site-Directed</term>
<term>Protein Binding</term>
<term>Protein Structure, Tertiary</term>
<term>Sequence Alignment</term>
<term>Sequence Analysis, DNA</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Alignement de séquences</term>
<term>Analyse de séquence d'ADN</term>
<term>Animaux</term>
<term>Cellules HeLa</term>
<term>Chiroptera</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Mutagenèse dirigée</term>
<term>Pénétration virale</term>
<term>Réservoirs d'agents pathogènes</term>
<term>Structure tertiaire des protéines</term>
<term>Substitution d'acide aminé</term>
<term>Séquence d'acides aminés</term>
<term>Variation génétique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>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
<italic>Myotis daubentoni</italic>
and
<italic>Rhinolophus sinicus</italic>
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
<italic>M. daubentoni</italic>
and
<italic>R. sinicus</italic>
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.</p>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1007/s00705-010-0729-6) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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</back>
</TEI>
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