Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.
Identifieur interne : 002145 ( Main/Exploration ); précédent : 002144; suivant : 002146Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.
Auteurs : Stephanie Bertram [Allemagne] ; Ilona Glowacka ; Marcel A. Müller ; Hayley Lavender ; Kerstin Gnirss ; Inga Nehlmeier ; Daniela Niemeyer ; Yuxian He ; Graham Simmons ; Christian Drosten ; Elizabeth J. Soilleux ; Olaf Jahn ; Imke Steffen ; Stefan PöhlmannSource :
- Journal of virology [ 1098-5514 ] ; 2011.
Descripteurs français
- KwdFr :
- Expression des gènes, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (métabolisme), Humains, Interactions hôte-pathogène, Lignée cellulaire, Peptidyl-Dipeptidase A (biosynthèse), Protéines de l'enveloppe virale (métabolisme), Protéolyse, Récepteurs viraux (biosynthèse), Serine endopeptidases (métabolisme), Virus du SRAS (pathogénicité).
- MESH :
- biosynthèse : Peptidyl-Dipeptidase A, Récepteurs viraux.
- métabolisme : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Serine endopeptidases.
- pathogénicité : Virus du SRAS.
- Expression des gènes, Glycoprotéine de spicule des coronavirus, Humains, Interactions hôte-pathogène, Lignée cellulaire, Protéolyse.
English descriptors
- KwdEn :
- Cell Line, Gene Expression, Host-Pathogen Interactions, Humans, Membrane Glycoproteins (metabolism), Peptidyl-Dipeptidase A (biosynthesis), Proteolysis, Receptors, Virus (biosynthesis), SARS Virus (pathogenicity), Serine Endopeptidases (metabolism), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (metabolism).
- MESH :
- chemical , biosynthesis : Peptidyl-Dipeptidase A, Receptors, Virus.
- chemical , metabolism : Membrane Glycoproteins, Serine Endopeptidases, Viral Envelope Proteins.
- pathogenicity : SARS Virus.
- Cell Line, Gene Expression, Host-Pathogen Interactions, Humans, Proteolysis, Spike Glycoprotein, Coronavirus.
Abstract
The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. The viral spike protein (SARS-S) mediates host cell entry and is a potential target for antiviral intervention. Activation of SARS-S by host cell proteases is essential for SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role of the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), in SARS-S activation. We found that HAT activates SARS-S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme 2 (ACE2) in bronchial epithelial cells and pneumocytes. HAT cleaved SARS-S at R667, as determined by mutagenesis and mass spectrometry, and activated SARS-S for cell-cell fusion in cis and trans, while the related pulmonary protease TMPRSS2 cleaved SARS-S at multiple sites and activated SARS-S only in trans. However, TMPRSS2 but not HAT expression rendered SARS-S-driven virus-cell fusion independent of cathepsin activity, indicating that HAT and TMPRSS2 activate SARS-S differentially. Collectively, our results show that HAT cleaves and activates SARS-S and might support viral spread in patients.
DOI: 10.1128/JVI.05300-11
PubMed: 21994442
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001462
- to stream PubMed, to step Curation: 001462
- to stream PubMed, to step Checkpoint: 001524
- to stream Ncbi, to step Merge: 002397
- to stream Ncbi, to step Curation: 002397
- to stream Ncbi, to step Checkpoint: 002397
- to stream Main, to step Merge: 002171
- to stream Main, to step Curation: 002145
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.</title><author><name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Virology, Hannover Medical School, Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name></author><author><name sortKey="Lavender, Hayley" sort="Lavender, Hayley" uniqKey="Lavender H" first="Hayley" last="Lavender">Hayley Lavender</name></author><author><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name></author><author><name sortKey="Nehlmeier, Inga" sort="Nehlmeier, Inga" uniqKey="Nehlmeier I" first="Inga" last="Nehlmeier">Inga Nehlmeier</name></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name></author><author><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name></author><author><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name></author><author><name sortKey="Soilleux, Elizabeth J" sort="Soilleux, Elizabeth J" uniqKey="Soilleux E" first="Elizabeth J" last="Soilleux">Elizabeth J. Soilleux</name></author><author><name sortKey="Jahn, Olaf" sort="Jahn, Olaf" uniqKey="Jahn O" first="Olaf" last="Jahn">Olaf Jahn</name></author><author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></author><author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21994442</idno><idno type="pmid">21994442</idno><idno type="doi">10.1128/JVI.05300-11</idno><idno type="wicri:Area/PubMed/Corpus">001462</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001462</idno><idno type="wicri:Area/PubMed/Curation">001462</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001462</idno><idno type="wicri:Area/PubMed/Checkpoint">001524</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001524</idno><idno type="wicri:Area/Ncbi/Merge">002397</idno><idno type="wicri:Area/Ncbi/Curation">002397</idno><idno type="wicri:Area/Ncbi/Checkpoint">002397</idno><idno type="wicri:Area/Main/Merge">002171</idno><idno type="wicri:Area/Main/Curation">002145</idno><idno type="wicri:Area/Main/Exploration">002145</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.</title><author><name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Virology, Hannover Medical School, Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name></author><author><name sortKey="Lavender, Hayley" sort="Lavender, Hayley" uniqKey="Lavender H" first="Hayley" last="Lavender">Hayley Lavender</name></author><author><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name></author><author><name sortKey="Nehlmeier, Inga" sort="Nehlmeier, Inga" uniqKey="Nehlmeier I" first="Inga" last="Nehlmeier">Inga Nehlmeier</name></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name></author><author><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name></author><author><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name></author><author><name sortKey="Soilleux, Elizabeth J" sort="Soilleux, Elizabeth J" uniqKey="Soilleux E" first="Elizabeth J" last="Soilleux">Elizabeth J. Soilleux</name></author><author><name sortKey="Jahn, Olaf" sort="Jahn, Olaf" uniqKey="Jahn O" first="Olaf" last="Jahn">Olaf Jahn</name></author><author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></author><author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line</term><term>Gene Expression</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Membrane Glycoproteins (metabolism)</term><term>Peptidyl-Dipeptidase A (biosynthesis)</term><term>Proteolysis</term><term>Receptors, Virus (biosynthesis)</term><term>SARS Virus (pathogenicity)</term><term>Serine Endopeptidases (metabolism)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Expression des gènes</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Peptidyl-Dipeptidase A (biosynthèse)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Protéolyse</term><term>Récepteurs viraux (biosynthèse)</term><term>Serine endopeptidases (métabolisme)</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Peptidyl-Dipeptidase A</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Glycoproteins</term><term>Serine Endopeptidases</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Serine endopeptidases</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Gene Expression</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Proteolysis</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Expression des gènes</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Protéolyse</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. The viral spike protein (SARS-S) mediates host cell entry and is a potential target for antiviral intervention. Activation of SARS-S by host cell proteases is essential for SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role of the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), in SARS-S activation. We found that HAT activates SARS-S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme 2 (ACE2) in bronchial epithelial cells and pneumocytes. HAT cleaved SARS-S at R667, as determined by mutagenesis and mass spectrometry, and activated SARS-S for cell-cell fusion in cis and trans, while the related pulmonary protease TMPRSS2 cleaved SARS-S at multiple sites and activated SARS-S only in trans. However, TMPRSS2 but not HAT expression rendered SARS-S-driven virus-cell fusion independent of cathepsin activity, indicating that HAT and TMPRSS2 activate SARS-S differentially. Collectively, our results show that HAT cleaves and activates SARS-S and might support viral spread in patients.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Basse-Saxe</li></region><settlement><li>Hanovre</li></settlement></list><tree><noCountry><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name><name sortKey="Jahn, Olaf" sort="Jahn, Olaf" uniqKey="Jahn O" first="Olaf" last="Jahn">Olaf Jahn</name><name sortKey="Lavender, Hayley" sort="Lavender, Hayley" uniqKey="Lavender H" first="Hayley" last="Lavender">Hayley Lavender</name><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><name sortKey="Nehlmeier, Inga" sort="Nehlmeier, Inga" uniqKey="Nehlmeier I" first="Inga" last="Nehlmeier">Inga Nehlmeier</name><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><name sortKey="Soilleux, Elizabeth J" sort="Soilleux, Elizabeth J" uniqKey="Soilleux E" first="Elizabeth J" last="Soilleux">Elizabeth J. Soilleux</name><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></noCountry><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002145 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002145 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:21994442
|texte= Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:21994442" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |