SrasV1, Main, Exploration, bibRecord, 002384

Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease

Identifieur interne : 002384 ( Main/Exploration ); précédent : 002383; suivant : 002385

Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease

Auteurs : Stephanie Bertram [Allemagne] ; Ilona Glowacka [Allemagne] ; Marcel A. Müller [Allemagne] ; Hayley Lavender [Royaume-Uni] ; Kerstin Gnirss [Allemagne] ; Inga Nehlmeier [Allemagne] ; Daniela Niemeyer [Allemagne] ; YUXIAN HE [République populaire de Chine] ; Graham Simmons [États-Unis] ; Christian Drosten [Allemagne] ; Elizabeth J. Soilleux [Royaume-Uni] ; Olaf Jahn [Allemagne] ; Imke Steffen [Allemagne, États-Unis] ; Stefan Pöhlmann [Allemagne]

Source :

Journal of virology [ 0022-538X ] ; 2011.

RBID : Pascal:12-0041035

Descripteurs français

Pascal (Inist)
- Coronavirus, Homme, Protéine, Voie respiratoire, Syndrome respiratoire aigu sévère.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Coronavirus, Human, Protein, Respiratory tract, Severe acute respiratory syndrome.

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.

Affiliations:

Links toward previous steps (curation, corpus...)

to stream PascalFrancis, to step Corpus: 000078
to stream PascalFrancis, to step Curation: 000909
to stream PascalFrancis, to step Checkpoint: 000106
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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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>
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</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
</author>
<author><name sortKey="Jahn, Olaf" sort="Jahn, Olaf" uniqKey="Jahn O" first="Olaf" last="Jahn">Olaf Jahn</name>
<affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Proteomics Group, Max Planck Institute of Experimental Medicine</s1>
<s2>Göttingen</s2>
<s3>DEU</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="2">Basse-Saxe</region>
<settlement type="city">Göttingen</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1>
<s2>Hannover</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="2">Basse-Saxe</region>
<settlement type="city">Hanovre</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Blood Systems Research Institute and Department of Laboratory Medicine, University of California</s1>
<s2>San Francisco, California</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</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"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1>
<s2>Hannover</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="2">Basse-Saxe</region>
<settlement type="city">Hanovre</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>German Primate Center</s1>
<s2>Göttingen</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="2">Basse-Saxe</region>
<settlement type="city">Göttingen</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term>
<term>Human</term>
<term>Protein</term>
<term>Respiratory tract</term>
<term>Severe acute respiratory syndrome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term>
<term>Homme</term>
<term>Protéine</term>
<term>Voie respiratoire</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</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>
<li>Royaume-Uni</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Basse-Saxe</li>
<li>Californie</li>
<li>District de Cologne</li>
<li>Oxfordshire</li>
<li>Rhénanie-du-Nord-Westphalie</li>
</region>
<settlement><li>Bonn</li>
<li>Göttingen</li>
<li>Hanovre</li>
<li>Oxford</li>
<li>Pékin</li>
</settlement>
<orgName><li>Université d'Oxford</li>
</orgName>
</list>
<tree><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>
<name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name>
<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="Jahn, Olaf" sort="Jahn, Olaf" uniqKey="Jahn O" first="Olaf" last="Jahn">Olaf Jahn</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="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
<name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Lavender, Hayley" sort="Lavender, Hayley" uniqKey="Lavender H" first="Hayley" last="Lavender">Hayley Lavender</name>
</region>
<name sortKey="Soilleux, Elizabeth J" sort="Soilleux, Elizabeth J" uniqKey="Soilleux E" first="Elizabeth J." last="Soilleux">Elizabeth J. Soilleux</name>
<name sortKey="Soilleux, Elizabeth J" sort="Soilleux, Elizabeth J" uniqKey="Soilleux E" first="Elizabeth J." last="Soilleux">Elizabeth J. Soilleux</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Yuxian He" sort="Yuxian He" uniqKey="Yuxian He" last="Yuxian He">YUXIAN HE</name>
</noRegion>
</country>
<country name="États-Unis"><region name="Californie"><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name>
</region>
<name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name>
</country>
</tree>
</affiliations>
</record>

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Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease

Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease

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