Abstract
Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.
MeSH terms
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Angiotensin-Converting Enzyme 2
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Animals
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Antibodies / immunology
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Antibodies / pharmacology
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Carboxypeptidases / antagonists & inhibitors
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Carboxypeptidases / genetics
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Carboxypeptidases / immunology
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Carboxypeptidases / metabolism
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Cell Line
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Chlorocebus aethiops
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Giant Cells / cytology
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Giant Cells / metabolism
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Humans
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Molecular Weight
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Peptidyl-Dipeptidase A / immunology
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Peptidyl-Dipeptidase A / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Receptors, Virus / antagonists & inhibitors
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Receptors, Virus / genetics
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Receptors, Virus / immunology
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Receptors, Virus / metabolism
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Severe acute respiratory syndrome-related coronavirus / genetics
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Severe acute respiratory syndrome-related coronavirus / growth & development
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Severe acute respiratory syndrome-related coronavirus / metabolism*
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Solubility
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Spike Glycoprotein, Coronavirus
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Transfection
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Vero Cells
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Viral Envelope Proteins / chemistry
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism
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Virus Replication / drug effects
Substances
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Antibodies
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Membrane Glycoproteins
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Receptors, Virus
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Spike Glycoprotein, Coronavirus
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Viral Envelope Proteins
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spike glycoprotein, SARS-CoV
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spike protein, mouse hepatitis virus
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Carboxypeptidases
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2