Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.
Identifieur interne : 002397 ( Ncbi/Curation ); précédent : 002396; suivant : 002398Cleavage 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
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pubmed:21994442Le document en format XML
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<term>Récepteurs viraux (biosynthèse)</term>
<term>Serine endopeptidases (métabolisme)</term>
<term>Virus du SRAS (pathogénicité)</term>
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<term>Host-Pathogen Interactions</term>
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<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>
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