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 : 002117 ( Main/Exploration ); précédent : 002116; suivant : 002118Evidence 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 ; Marcel A. Müller ; Paul Allen ; Elizabeth Soilleux ; Susanne Pfefferle ; Imke Steffen ; Theodros Solomon Tsegaye ; Yuxian He ; Kerstin Gnirss ; Daniela Niemeyer ; Heike Schneider ; Christian Drosten ; Stefan PöhlmannSource :
- Journal of virology [ 1098-5514 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Glycoprotéines membranaires (métabolisme), Humains, Immunité humorale, Interactions hôte-pathogène, Lignée cellulaire, Protéines de l'enveloppe virale (immunologie), Protéines de l'enveloppe virale (métabolisme), Pénétration virale, Serine endopeptidases (métabolisme), Technique de Western, Virus du SRAS (immunologie), Virus du SRAS (pathogénicité).
- MESH :
- immunologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus du SRAS.
- métabolisme : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Serine endopeptidases.
- pathogénicité : Virus du SRAS.
- Animaux, Glycoprotéine de spicule des coronavirus, Humains, Immunité humorale, Interactions hôte-pathogène, Lignée cellulaire, Pénétration virale, Technique de Western.
English descriptors
- KwdEn :
- Animals, Blotting, Western, Cell Line, Host-Pathogen Interactions, Humans, Immunity, Humoral, Membrane Glycoproteins (immunology), Membrane Glycoproteins (metabolism), SARS Virus (immunology), SARS Virus (pathogenicity), Serine Endopeptidases (metabolism), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (immunology), Viral Envelope Proteins (metabolism), Virus Internalization.
- MESH :
- chemical , immunology : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Membrane Glycoproteins, Serine Endopeptidases, Viral Envelope Proteins.
- immunology : SARS Virus.
- pathogenicity : SARS Virus.
- Animals, Blotting, Western, Cell Line, Host-Pathogen Interactions, Humans, Immunity, Humoral, Spike Glycoprotein, Coronavirus, Virus Internalization.
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.
DOI: 10.1128/JVI.02232-10
PubMed: 21325420
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001548
- to stream PubMed, to step Curation: 001548
- to stream PubMed, to step Checkpoint: 001498
- to stream Ncbi, to step Merge: 002295
- to stream Ncbi, to step Curation: 002295
- to stream Ncbi, to step Checkpoint: 002295
- to stream Main, to step Merge: 002143
- to stream Main, to step Curation: 002117
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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"><nlm:affiliation>Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Hannover Medical School, 30625 Hannover</wicri:regionArea><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></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="Allen, Paul" sort="Allen, Paul" uniqKey="Allen P" first="Paul" last="Allen">Paul Allen</name></author><author><name sortKey="Soilleux, Elizabeth" sort="Soilleux, Elizabeth" uniqKey="Soilleux E" first="Elizabeth" last="Soilleux">Elizabeth Soilleux</name></author><author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name></author><author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></author><author><name sortKey="Tsegaye, Theodros Solomon" sort="Tsegaye, Theodros Solomon" uniqKey="Tsegaye T" first="Theodros Solomon" last="Tsegaye">Theodros Solomon Tsegaye</name></author><author><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name></author><author><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name></author><author><name sortKey="Schneider, Heike" sort="Schneider, Heike" uniqKey="Schneider H" first="Heike" last="Schneider">Heike Schneider</name></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</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:21325420</idno><idno type="pmid">21325420</idno><idno type="doi">10.1128/JVI.02232-10</idno><idno type="wicri:Area/PubMed/Corpus">001548</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001548</idno><idno type="wicri:Area/PubMed/Curation">001548</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001548</idno><idno type="wicri:Area/PubMed/Checkpoint">001498</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001498</idno><idno type="wicri:Area/Ncbi/Merge">002295</idno><idno type="wicri:Area/Ncbi/Curation">002295</idno><idno type="wicri:Area/Ncbi/Checkpoint">002295</idno><idno type="wicri:Area/Main/Merge">002143</idno><idno type="wicri:Area/Main/Curation">002117</idno><idno type="wicri:Area/Main/Exploration">002117</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">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"><nlm:affiliation>Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology, Hannover Medical School, 30625 Hannover</wicri:regionArea><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></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="Allen, Paul" sort="Allen, Paul" uniqKey="Allen P" first="Paul" last="Allen">Paul Allen</name></author><author><name sortKey="Soilleux, Elizabeth" sort="Soilleux, Elizabeth" uniqKey="Soilleux E" first="Elizabeth" last="Soilleux">Elizabeth Soilleux</name></author><author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name></author><author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></author><author><name sortKey="Tsegaye, Theodros Solomon" sort="Tsegaye, Theodros Solomon" uniqKey="Tsegaye T" first="Theodros Solomon" last="Tsegaye">Theodros Solomon Tsegaye</name></author><author><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name></author><author><name sortKey="Gnirss, Kerstin" sort="Gnirss, Kerstin" uniqKey="Gnirss K" first="Kerstin" last="Gnirss">Kerstin Gnirss</name></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name></author><author><name sortKey="Schneider, Heike" sort="Schneider, Heike" uniqKey="Schneider H" first="Heike" last="Schneider">Heike Schneider</name></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</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>Animals</term><term>Blotting, Western</term><term>Cell Line</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Immunity, Humoral</term><term>Membrane Glycoproteins (immunology)</term><term>Membrane Glycoproteins (metabolism)</term><term>SARS Virus (immunology)</term><term>SARS Virus (pathogenicity)</term><term>Serine Endopeptidases (metabolism)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (immunology)</term><term>Viral Envelope Proteins (metabolism)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (immunologie)</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Humains</term><term>Immunité humorale</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Pénétration virale</term><term>Serine endopeptidases (métabolisme)</term><term>Technique de Western</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (pathogénicité)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</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="immunologie" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</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>Animals</term><term>Blotting, Western</term><term>Cell Line</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Immunity, Humoral</term><term>Spike Glycoprotein, Coronavirus</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Immunité humorale</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Pénétration virale</term><term>Technique de Western</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></country><region><li>Basse-Saxe</li></region><settlement><li>Hanovre</li></settlement></list><tree><noCountry><name sortKey="Allen, Paul" sort="Allen, Paul" uniqKey="Allen P" first="Paul" last="Allen">Paul Allen</name><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="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</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="Schneider, Heike" sort="Schneider, Heike" uniqKey="Schneider H" first="Heike" last="Schneider">Heike Schneider</name><name sortKey="Soilleux, Elizabeth" sort="Soilleux, Elizabeth" uniqKey="Soilleux E" first="Elizabeth" last="Soilleux">Elizabeth Soilleux</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></noCountry><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></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 002117 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002117 | 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:21325420
|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.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:21325420" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |