Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion
- Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA (United States)
- Institute of Virology, Hannover Medical School, 30625 Hannover (Germany)
- Institute for Virology, University Hospital Erlangen, 91054 Erlangen (Germany)
- Department of Microbiology, University of Pennsylvania, PA 19104-6076 (United States)
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.
- OSTI ID:
- 21486934
- Journal Information:
- Virology, Vol. 413, Issue 2; Other Information: DOI: 10.1016/j.virol.2011.02.020; PII: S0042-6822(11)00092-4; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
Similar Records
Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity
Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain