SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.
Identifieur interne : 003D31 ( Main/Exploration ); précédent : 003D30; suivant : 003D32SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.
Auteurs : I-Chueh Huang [États-Unis] ; Berend Jan Bosch ; Fang Li ; Wenhui Li ; Kyoung Hoa Lee ; Sorina Ghiran ; Natalya Vasilieva ; Terence S. Dermody ; Stephen C. Harrison ; Philip R. Dormitzer ; Michael Farzan ; Peter J M. Rottier ; Hyeryun ChoeSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2006.
Descripteurs français
- KwdFr :
- Animaux, Carboxypeptidases (métabolisme), Cathepsine L, Cathepsines (métabolisme), Cathepsines (physiologie), Cellules Vero, Coronavirus (physiologie), Cysteine endopeptidases (métabolisme), Cysteine endopeptidases (physiologie), Endosomes (métabolisme), Glycoprotéines membranaires (métabolisme), Humains, Lignée cellulaire, Lysosomes (enzymologie), Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale (métabolisme), Protéines à fluorescence verte (métabolisme), Retroviridae (génétique), Spécificité d'espèce, Virus du SRAS (physiologie).
- MESH :
- enzymologie : Lysosomes.
- génétique : Retroviridae.
- métabolisme : Carboxypeptidases, Cathepsines, Cysteine endopeptidases, Endosomes, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Protéines à fluorescence verte.
- physiologie : Cathepsines, Coronavirus, Cysteine endopeptidases, Virus du SRAS.
- Animaux, Cathepsine L, Cellules Vero, Humains, Lignée cellulaire, Peptidyl-Dipeptidase A, Spécificité d'espèce.
English descriptors
- KwdEn :
- Animals, Carboxypeptidases (metabolism), Cathepsin L, Cathepsins (metabolism), Cathepsins (physiology), Cell Line, Chlorocebus aethiops, Coronavirus (physiology), Cysteine Endopeptidases (metabolism), Cysteine Endopeptidases (physiology), Endosomes (metabolism), Green Fluorescent Proteins (metabolism), Humans, Lysosomes (enzymology), Membrane Glycoproteins (metabolism), Peptidyl-Dipeptidase A, Retroviridae (genetics), SARS Virus (physiology), Species Specificity, Vero Cells, Viral Envelope Proteins (metabolism).
- MESH :
- chemical , metabolism : Carboxypeptidases, Cathepsins, Cysteine Endopeptidases, Green Fluorescent Proteins, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , physiology : Cathepsins, Cysteine Endopeptidases.
- enzymology : Lysosomes.
- genetics : Retroviridae.
- metabolism : Endosomes.
- physiology : Coronavirus, SARS Virus.
- Animals, Cathepsin L, Cell Line, Chlorocebus aethiops, Humans, Peptidyl-Dipeptidase A, Species Specificity, Vero Cells.
Abstract
Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.
DOI: 10.1074/jbc.M508381200
PubMed: 16339146
Affiliations:
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Le document en format XML
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<term>Cathepsins (metabolism)</term>
<term>Cathepsins (physiology)</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Coronavirus (physiology)</term>
<term>Cysteine Endopeptidases (metabolism)</term>
<term>Cysteine Endopeptidases (physiology)</term>
<term>Endosomes (metabolism)</term>
<term>Green Fluorescent Proteins (metabolism)</term>
<term>Humans</term>
<term>Lysosomes (enzymology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Peptidyl-Dipeptidase A</term>
<term>Retroviridae (genetics)</term>
<term>SARS Virus (physiology)</term>
<term>Species Specificity</term>
<term>Vero Cells</term>
<term>Viral Envelope Proteins (metabolism)</term>
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<term>Carboxypeptidases (métabolisme)</term>
<term>Cathepsine L</term>
<term>Cathepsines (métabolisme)</term>
<term>Cathepsines (physiologie)</term>
<term>Cellules Vero</term>
<term>Coronavirus (physiologie)</term>
<term>Cysteine endopeptidases (métabolisme)</term>
<term>Cysteine endopeptidases (physiologie)</term>
<term>Endosomes (métabolisme)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Lysosomes (enzymologie)</term>
<term>Peptidyl-Dipeptidase A</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Protéines à fluorescence verte (métabolisme)</term>
<term>Retroviridae (génétique)</term>
<term>Spécificité d'espèce</term>
<term>Virus du SRAS (physiologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carboxypeptidases</term>
<term>Cathepsins</term>
<term>Cysteine Endopeptidases</term>
<term>Green Fluorescent Proteins</term>
<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
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<term>Cysteine Endopeptidases</term>
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<term>Cathepsines</term>
<term>Cysteine endopeptidases</term>
<term>Endosomes</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines à fluorescence verte</term>
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<term>Coronavirus</term>
<term>Cysteine endopeptidases</term>
<term>Virus du SRAS</term>
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<front><div type="abstract" xml:lang="en">Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.</div>
</front>
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<affiliations><list><country><li>États-Unis</li>
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<tree><noCountry><name sortKey="Bosch, Berend Jan" sort="Bosch, Berend Jan" uniqKey="Bosch B" first="Berend Jan" last="Bosch">Berend Jan Bosch</name>
<name sortKey="Choe, Hyeryun" sort="Choe, Hyeryun" uniqKey="Choe H" first="Hyeryun" last="Choe">Hyeryun Choe</name>
<name sortKey="Dermody, Terence S" sort="Dermody, Terence S" uniqKey="Dermody T" first="Terence S" last="Dermody">Terence S. Dermody</name>
<name sortKey="Dormitzer, Philip R" sort="Dormitzer, Philip R" uniqKey="Dormitzer P" first="Philip R" last="Dormitzer">Philip R. Dormitzer</name>
<name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name>
<name sortKey="Ghiran, Sorina" sort="Ghiran, Sorina" uniqKey="Ghiran S" first="Sorina" last="Ghiran">Sorina Ghiran</name>
<name sortKey="Harrison, Stephen C" sort="Harrison, Stephen C" uniqKey="Harrison S" first="Stephen C" last="Harrison">Stephen C. Harrison</name>
<name sortKey="Lee, Kyoung Hoa" sort="Lee, Kyoung Hoa" uniqKey="Lee K" first="Kyoung Hoa" last="Lee">Kyoung Hoa Lee</name>
<name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<name sortKey="Li, Wenhui" sort="Li, Wenhui" uniqKey="Li W" first="Wenhui" last="Li">Wenhui Li</name>
<name sortKey="Rottier, Peter J M" sort="Rottier, Peter J M" uniqKey="Rottier P" first="Peter J M" last="Rottier">Peter J M. Rottier</name>
<name sortKey="Vasilieva, Natalya" sort="Vasilieva, Natalya" uniqKey="Vasilieva N" first="Natalya" last="Vasilieva">Natalya Vasilieva</name>
</noCountry>
<country name="États-Unis"><noRegion><name sortKey="Huang, I Chueh" sort="Huang, I Chueh" uniqKey="Huang I" first="I-Chueh" last="Huang">I-Chueh Huang</name>
</noRegion>
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