Document Detail


Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion.
MedLine Citation:
PMID:  21435673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Graham Simmons; Stephanie Bertram; Ilona Glowacka; Imke Steffen; Chawaree Chaipan; Juliet Agudelo; Kai Lu; Andrew J Rennekamp; Heike Hofmann; Paul Bates; Stefan Pöhlmann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-23
Journal Detail:
Title:  Virology     Volume:  413     ISSN:  1096-0341     ISO Abbreviation:  Virology     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-19     Completed Date:  2011-06-23     Revised Date:  2014-04-03    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  265-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Cell Fusion
Cell Line
Furin / genetics,  metabolism
Gene Expression Regulation, Viral / physiology
Humans
Leupeptins
Mutation
Peptide Hydrolases / metabolism*
SARS Virus / physiology*
Trypsin
Virus Internalization
Grant Support
ID/Acronym/Agency:
R01 AI074986-02/AI/NIAID NIH HHS; R01 AI074986-05/AI/NIAID NIH HHS; R21 AI059172/AI/NIAID NIH HHS; R21 AI059172/AI/NIAID NIH HHS; U01 AI070369/AI/NIAID NIH HHS; U54 AI57168/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Leupeptins; EC 3.4.-/Peptide Hydrolases; EC 3.4.21.4/Trypsin; EC 3.4.21.75/Furin; J97339NR3V/leupeptin
Comments/Corrections

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