Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response
Identifieur interne : 002375 ( Main/Exploration ); précédent : 002374; suivant : 002376Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response
Auteurs : Ilona Glowacka [Allemagne] ; Stephanie Bertram [Allemagne] ; Marcel A. Müller [Allemagne] ; Paul Allen [Royaume-Uni] ; Elizabeth Soilleux [Royaume-Uni] ; Susanne Pfefferle [Allemagne] ; Imke Steffen [Allemagne] ; Theodros Solomon Tsegaye [Allemagne] ; YUXIAN HE [République populaire de Chine] ; Kerstin Gnirss [Allemagne] ; Daniela Niemeyer [Allemagne] ; Heike Schneider [Allemagne] ; Christian Drosten [Allemagne] ; Stefan Pöhlmann [Allemagne]Source :
- Journal of virology [ 0022-538X ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave SARS S. We along with others could previously show that the type II transmembrane protease TMPRSS2 activates the influenza virus hemagglutinin and the human metapneumovirus F protein by cleavage. Here, we assessed whether SARS S is proteolytically processed by TMPRSS2. Western blot analysis revealed that SARS S was cleaved into several fragments upon coexpression of TMPRSS2 (cis-cleavage) and upon contact between SARS S-expressing cells and TMPRSS2-positive cells (trans-cleavage). cis-cleavage resulted in release of SARS S fragments into the cellular supernatant and in inhibition of antibody-mediated neutralization, most likely because SARS S fragments function as antibody decoys. trans-cleavage activated SARS S on effector cells for fusion with target cells and allowed efficient SARS S-driven viral entry into targets treated with a lysosomotropic agent or a cathepsin inhibitor. Finally, ACE2, the cellular receptor for SARS-CoV, and TMPRSS2 were found to be coexpressed by type II pneumocytes, which represent important viral target cells, suggesting that SARS S is cleaved by TMPRSS2 in the lung of SARS-CoV-infected individuals. In summary, we show that TMPRSS2 might promote viral spread and pathogenesis by diminishing viral recognition by neutralizing antibodies and by activating SARS S for cell-cell and virus-cell fusion.
Affiliations:
- Allemagne, Royaume-Uni, République populaire de Chine
- Basse-Saxe, District de Cologne, Hambourg, Rhénanie-du-Nord-Westphalie
- Bonn, Göttingen, Hambourg, Hanovre, Pékin
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 000109
- to stream PascalFrancis, to step Curation: 000879
- to stream PascalFrancis, to step Checkpoint: 000096
- to stream Main, to step Merge: 002403
- to stream Main, to step Curation: 002375
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response</title><author><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Virology, University of Bonn Medical Centre</s1><s2>53127 Bonn</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Allen, Paul" sort="Allen, Paul" uniqKey="Allen P" first="Paul" last="Allen">Paul Allen</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Cellular Pathology, John Radclif<sup>f</sup>e Hospital</s1><s2>Oxford OX3 9DU</s2><s3>GBR</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Oxford OX3 9DU</wicri:noRegion></affiliation></author><author><name sortKey="Soilleux, Elizabeth" sort="Soilleux, Elizabeth" uniqKey="Soilleux E" first="Elizabeth" last="Soilleux">Elizabeth Soilleux</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Cellular Pathology, John Radclif<sup>f</sup>e Hospital</s1><s2>Oxford OX3 9DU</s2><s3>GBR</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Oxford OX3 9DU</wicri:noRegion></affiliation></author><author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Bernhard Nocht Institute for Tropical Medicine</s1><s2>20359 Hamburg</s2><s3>DEU</s3><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>20359 Hamburg</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></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>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Tsegaye, Theodros Solomon" sort="Tsegaye, Theodros Solomon" uniqKey="Tsegaye T" first="Theodros Solomon" last="Tsegaye">Theodros Solomon Tsegaye</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Yuxian He" sort="Yuxian He" uniqKey="Yuxian He" last="Yuxian He">YUXIAN HE</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College</s1><s2>Beijing 1007302</s2><s3>CHN</s3><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Virology, University of Bonn Medical Centre</s1><s2>53127 Bonn</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Schneider, Heike" sort="Schneider, Heike" uniqKey="Schneider H" first="Heike" last="Schneider">Heike Schneider</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Institute for Physiological Chemistry, Hannover Medical School</s1><s2>30625 Hannover</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">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Virology, University of Bonn Medical Centre</s1><s2>53127 Bonn</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</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"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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="07"><s1>German Primate Center, Kellnerweg 4</s1><s2>37077 Göttingen</s2><s3>DEU</s3><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></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0240923</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0240923 INIST</idno><idno type="RBID">Pascal:11-0240923</idno><idno type="wicri:Area/PascalFrancis/Corpus">000109</idno><idno type="wicri:Area/PascalFrancis/Curation">000879</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000096</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000096</idno><idno type="wicri:doubleKey">0022-538X:2011:Glowacka I:evidence:that:tmprss</idno><idno type="wicri:Area/Main/Merge">002403</idno><idno type="wicri:Area/Main/Curation">002375</idno><idno type="wicri:Area/Main/Exploration">002375</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response</title><author><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Virology, University of Bonn Medical Centre</s1><s2>53127 Bonn</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Allen, Paul" sort="Allen, Paul" uniqKey="Allen P" first="Paul" last="Allen">Paul Allen</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Cellular Pathology, John Radclif<sup>f</sup>e Hospital</s1><s2>Oxford OX3 9DU</s2><s3>GBR</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Oxford OX3 9DU</wicri:noRegion></affiliation></author><author><name sortKey="Soilleux, Elizabeth" sort="Soilleux, Elizabeth" uniqKey="Soilleux E" first="Elizabeth" last="Soilleux">Elizabeth Soilleux</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Cellular Pathology, John Radclif<sup>f</sup>e Hospital</s1><s2>Oxford OX3 9DU</s2><s3>GBR</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Oxford OX3 9DU</wicri:noRegion></affiliation></author><author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Bernhard Nocht Institute for Tropical Medicine</s1><s2>20359 Hamburg</s2><s3>DEU</s3><sZ>6 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>20359 Hamburg</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></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>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Tsegaye, Theodros Solomon" sort="Tsegaye, Theodros Solomon" uniqKey="Tsegaye T" first="Theodros Solomon" last="Tsegaye">Theodros Solomon Tsegaye</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Yuxian He" sort="Yuxian He" uniqKey="Yuxian He" last="Yuxian He">YUXIAN HE</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College</s1><s2>Beijing 1007302</s2><s3>CHN</s3><sZ>9 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Virology, University of Bonn Medical Centre</s1><s2>53127 Bonn</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Schneider, Heike" sort="Schneider, Heike" uniqKey="Schneider H" first="Heike" last="Schneider">Heike Schneider</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Institute for Physiological Chemistry, Hannover Medical School</s1><s2>30625 Hannover</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">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Virology, University of Bonn Medical Centre</s1><s2>53127 Bonn</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</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"><inist:fA14 i1="01"><s1>Institute of Virology, Hannover Medical School</s1><s2>30625 Hannover</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>10 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="07"><s1>German Primate Center, Kellnerweg 4</s1><s2>37077 Göttingen</s2><s3>DEU</s3><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>Fusion protein</term><term>Humoral immunity</term><term>Immune response</term><term>Membrane protein</term><term>Severe acute respiratory syndrome</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Protéine membranaire</term><term>Protéine fusion</term><term>Immunité humorale</term><term>Réponse immune</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave SARS S. We along with others could previously show that the type II transmembrane protease TMPRSS2 activates the influenza virus hemagglutinin and the human metapneumovirus F protein by cleavage. Here, we assessed whether SARS S is proteolytically processed by TMPRSS2. Western blot analysis revealed that SARS S was cleaved into several fragments upon coexpression of TMPRSS2 (cis-cleavage) and upon contact between SARS S-expressing cells and TMPRSS2-positive cells (trans-cleavage). cis-cleavage resulted in release of SARS S fragments into the cellular supernatant and in inhibition of antibody-mediated neutralization, most likely because SARS S fragments function as antibody decoys. trans-cleavage activated SARS S on effector cells for fusion with target cells and allowed efficient SARS S-driven viral entry into targets treated with a lysosomotropic agent or a cathepsin inhibitor. Finally, ACE2, the cellular receptor for SARS-CoV, and TMPRSS2 were found to be coexpressed by type II pneumocytes, which represent important viral target cells, suggesting that SARS S is cleaved by TMPRSS2 in the lung of SARS-CoV-infected individuals. In summary, we show that TMPRSS2 might promote viral spread and pathogenesis by diminishing viral recognition by neutralizing antibodies and by activating SARS S for cell-cell and virus-cell fusion.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li><li>République populaire de Chine</li></country><region><li>Basse-Saxe</li><li>District de Cologne</li><li>Hambourg</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Bonn</li><li>Göttingen</li><li>Hambourg</li><li>Hanovre</li><li>Pékin</li></settlement></list><tree><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</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="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</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="Schneider, Heike" sort="Schneider, Heike" uniqKey="Schneider H" first="Heike" last="Schneider">Heike Schneider</name><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name><name sortKey="Tsegaye, Theodros Solomon" sort="Tsegaye, Theodros Solomon" uniqKey="Tsegaye T" first="Theodros Solomon" last="Tsegaye">Theodros Solomon Tsegaye</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Allen, Paul" sort="Allen, Paul" uniqKey="Allen P" first="Paul" last="Allen">Paul Allen</name></noRegion><name sortKey="Soilleux, Elizabeth" sort="Soilleux, Elizabeth" uniqKey="Soilleux E" first="Elizabeth" last="Soilleux">Elizabeth 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></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 002375 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002375 | 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= Pascal:11-0240923
|texte= Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response
}}
| This area was generated with Dilib version V0.6.33. |  |