Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion.
Identifieur interne : 002127 ( Main/Exploration ); précédent : 002126; suivant : 002128Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion.
Auteurs : Graham Simmons [États-Unis] ; Stephanie Bertram ; Ilona Glowacka ; Imke Steffen ; Chawaree Chaipan ; Juliet Agudelo ; Kai Lu ; Andrew J. Rennekamp ; Heike Hofmann ; Paul Bates ; Stefan PöhlmannSource :
- Virology [ 1096-0341 ] ; 2011.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Furine.
- métabolisme : Furine, Peptide hydrolases.
- physiologie : Régulation de l'expression des gènes viraux, Virus du SRAS.
- Fusion cellulaire, Humains, Leupeptines, Lignée cellulaire, Mutation, Pénétration virale, Trypsine.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Furin.
- chemical , metabolism : Furin, Peptide Hydrolases.
- physiology : Gene Expression Regulation, Viral, SARS Virus.
- Cell Fusion, Cell Line, Humans, Leupeptins, Mutation, Trypsin, Virus Internalization.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.
DOI: 10.1016/j.virol.2011.02.020
PubMed: 21435673
Affiliations:
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Rennekamp</name></author><author><name sortKey="Hofmann, Heike" sort="Hofmann, Heike" uniqKey="Hofmann H" first="Heike" last="Hofmann">Heike Hofmann</name></author><author><name sortKey="Bates, Paul" sort="Bates, Paul" uniqKey="Bates P" first="Paul" last="Bates">Paul Bates</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:21435673</idno><idno type="pmid">21435673</idno><idno type="doi">10.1016/j.virol.2011.02.020</idno><idno type="wicri:Area/PubMed/Corpus">001531</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001531</idno><idno type="wicri:Area/PubMed/Curation">001531</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001531</idno><idno type="wicri:Area/PubMed/Checkpoint">001507</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001507</idno><idno type="wicri:Area/Ncbi/Merge">002319</idno><idno type="wicri:Area/Ncbi/Curation">002319</idno><idno type="wicri:Area/Ncbi/Checkpoint">002319</idno><idno type="wicri:Area/Main/Merge">002153</idno><idno type="wicri:Area/Main/Curation">002127</idno><idno type="wicri:Area/Main/Exploration">002127</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion.</title><author><name sortKey="Simmons, Graham" sort="Simmons, Graham" uniqKey="Simmons G" first="Graham" last="Simmons">Graham Simmons</name><affiliation wicri:level="2"><nlm:affiliation>Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA, USA. gsimmons@bloodsystems.org</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></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="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name></author><author><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></author><author><name sortKey="Chaipan, Chawaree" sort="Chaipan, Chawaree" uniqKey="Chaipan C" first="Chawaree" last="Chaipan">Chawaree Chaipan</name></author><author><name sortKey="Agudelo, Juliet" sort="Agudelo, Juliet" uniqKey="Agudelo J" first="Juliet" last="Agudelo">Juliet Agudelo</name></author><author><name sortKey="Lu, Kai" sort="Lu, Kai" uniqKey="Lu K" first="Kai" last="Lu">Kai Lu</name></author><author><name sortKey="Rennekamp, Andrew J" sort="Rennekamp, Andrew J" uniqKey="Rennekamp A" first="Andrew J" last="Rennekamp">Andrew J. Rennekamp</name></author><author><name sortKey="Hofmann, Heike" sort="Hofmann, Heike" uniqKey="Hofmann H" first="Heike" last="Hofmann">Heike Hofmann</name></author><author><name sortKey="Bates, Paul" sort="Bates, Paul" uniqKey="Bates P" first="Paul" last="Bates">Paul Bates</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">Virology</title><idno type="eISSN">1096-0341</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Fusion</term><term>Cell Line</term><term>Furin (genetics)</term><term>Furin (metabolism)</term><term>Gene Expression Regulation, Viral (physiology)</term><term>Humans</term><term>Leupeptins</term><term>Mutation</term><term>Peptide Hydrolases (metabolism)</term><term>SARS Virus (physiology)</term><term>Trypsin</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Furine (génétique)</term><term>Furine (métabolisme)</term><term>Fusion cellulaire</term><term>Humains</term><term>Leupeptines</term><term>Lignée cellulaire</term><term>Mutation</term><term>Peptide hydrolases (métabolisme)</term><term>Pénétration virale</term><term>Régulation de l'expression des gènes viraux (physiologie)</term><term>Trypsine</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Furin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Furin</term><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Furine</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Furine</term><term>Peptide hydrolases</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Régulation de l'expression des gènes viraux</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Gene Expression Regulation, Viral</term><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Fusion</term><term>Cell Line</term><term>Humans</term><term>Leupeptins</term><term>Mutation</term><term>Trypsin</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Fusion cellulaire</term><term>Humains</term><term>Leupeptines</term><term>Lignée cellulaire</term><term>Mutation</term><term>Pénétration virale</term><term>Trypsine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><noCountry><name sortKey="Agudelo, Juliet" sort="Agudelo, Juliet" uniqKey="Agudelo J" first="Juliet" last="Agudelo">Juliet Agudelo</name><name sortKey="Bates, Paul" sort="Bates, Paul" uniqKey="Bates P" first="Paul" last="Bates">Paul Bates</name><name sortKey="Bertram, Stephanie" sort="Bertram, Stephanie" uniqKey="Bertram S" first="Stephanie" last="Bertram">Stephanie Bertram</name><name sortKey="Chaipan, Chawaree" sort="Chaipan, Chawaree" uniqKey="Chaipan C" first="Chawaree" last="Chaipan">Chawaree Chaipan</name><name sortKey="Glowacka, Ilona" sort="Glowacka, Ilona" uniqKey="Glowacka I" first="Ilona" last="Glowacka">Ilona Glowacka</name><name sortKey="Hofmann, Heike" sort="Hofmann, Heike" uniqKey="Hofmann H" first="Heike" last="Hofmann">Heike Hofmann</name><name sortKey="Lu, Kai" sort="Lu, Kai" uniqKey="Lu K" first="Kai" last="Lu">Kai Lu</name><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><name sortKey="Rennekamp, Andrew J" sort="Rennekamp, Andrew J" uniqKey="Rennekamp A" first="Andrew J" last="Rennekamp">Andrew J. Rennekamp</name><name sortKey="Steffen, Imke" sort="Steffen, Imke" uniqKey="Steffen I" first="Imke" last="Steffen">Imke Steffen</name></noCountry><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></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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