Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.
Identifieur interne : 000E55 ( Main/Exploration ); précédent : 000E54; suivant : 000E56Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.
Auteurs : Lennart Michel Reinke [Allemagne] ; Martin Spiegel [Allemagne] ; Teresa Plegge [Allemagne] ; Anika Hartleib [Allemagne] ; Inga Nehlmeier [Allemagne] ; Stefanie Gierer [Allemagne] ; Markus Hoffmann [Allemagne] ; Heike Hofmann-Winkler [Allemagne] ; Michael Winkler [Allemagne] ; Stefan Pöhlmann [Allemagne]Source :
- PloS one [ 1932-6203 ] ; 2017.
Descripteurs français
- KwdFr :
- Cellules HEK293, Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Interactions hôte-pathogène, Mutation (génétique), Pénétration virale, Serine endopeptidases (génétique), Serine endopeptidases (métabolisme), Transport de protéines.
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Serine Endopeptidases, Spike Glycoprotein, Coronavirus.
- genetics : Mutation.
- chemical , metabolism : Serine Endopeptidases, Spike Glycoprotein, Coronavirus.
- HEK293 Cells, Host-Pathogen Interactions, Humans, Protein Transport, Virus Internalization.
Abstract
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.
DOI: 10.1371/journal.pone.0179177
PubMed: 28636671
Affiliations:
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xml:lang="en">Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.</title><author><name sortKey="Reinke, Lennart Michel" sort="Reinke, Lennart Michel" uniqKey="Reinke L" first="Lennart Michel" last="Reinke">Lennart Michel Reinke</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Spiegel, Martin" sort="Spiegel, Martin" uniqKey="Spiegel M" first="Martin" last="Spiegel">Martin Spiegel</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, 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Hartleib</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Nehlmeier, Inga" sort="Nehlmeier, Inga" uniqKey="Nehlmeier I" first="Inga" last="Nehlmeier">Inga Nehlmeier</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Gierer, Stefanie" sort="Gierer, Stefanie" uniqKey="Gierer S" first="Stefanie" last="Gierer">Stefanie Gierer</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Hoffmann, Markus" sort="Hoffmann, Markus" uniqKey="Hoffmann M" first="Markus" last="Hoffmann">Markus Hoffmann</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, 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Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author><author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><affiliation wicri:level="3"><nlm:affiliation>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abteilung Infektionsbiologie, Deutsches Primatenzentrum, Göttingen</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Göttingen</settlement></placeName></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>HEK293 Cells</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Mutation (genetics)</term><term>Protein Transport</term><term>Serine Endopeptidases (genetics)</term><term>Serine Endopeptidases (metabolism)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HEK293</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Mutation (génétique)</term><term>Pénétration virale</term><term>Serine endopeptidases (génétique)</term><term>Serine endopeptidases (métabolisme)</term><term>Transport de protéines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Serine Endopeptidases</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Mutation</term><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Serine Endopeptidases</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>HEK293 Cells</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Protein Transport</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HEK293</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Pénétration virale</term><term>Transport de protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Basse-Saxe</li></region><settlement><li>Göttingen</li></settlement></list><tree><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Reinke, Lennart Michel" sort="Reinke, Lennart Michel" uniqKey="Reinke L" first="Lennart Michel" last="Reinke">Lennart Michel Reinke</name></region><name sortKey="Gierer, Stefanie" sort="Gierer, Stefanie" uniqKey="Gierer S" first="Stefanie" last="Gierer">Stefanie Gierer</name><name sortKey="Hartleib, Anika" sort="Hartleib, Anika" uniqKey="Hartleib A" first="Anika" last="Hartleib">Anika Hartleib</name><name sortKey="Hoffmann, Markus" sort="Hoffmann, Markus" uniqKey="Hoffmann M" first="Markus" last="Hoffmann">Markus Hoffmann</name><name sortKey="Hofmann Winkler, Heike" sort="Hofmann Winkler, Heike" uniqKey="Hofmann Winkler H" first="Heike" last="Hofmann-Winkler">Heike Hofmann-Winkler</name><name sortKey="Nehlmeier, Inga" sort="Nehlmeier, Inga" uniqKey="Nehlmeier I" first="Inga" last="Nehlmeier">Inga Nehlmeier</name><name sortKey="Plegge, Teresa" sort="Plegge, Teresa" uniqKey="Plegge T" first="Teresa" last="Plegge">Teresa Plegge</name><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><name sortKey="Spiegel, Martin" sort="Spiegel, Martin" uniqKey="Spiegel M" first="Martin" last="Spiegel">Martin Spiegel</name><name sortKey="Winkler, Michael" sort="Winkler, Michael" uniqKey="Winkler M" first="Michael" last="Winkler">Michael Winkler</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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