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Virology. 2011 May 10;413(2):265-74. doi: 10.1016/j.virol.2011.02.020. Epub 2011 Mar 23.

Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion.

Author information

1
Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA, USA. gsimmons@bloodsystems.org

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.

PMID:
21435673
PMCID:
PMC3086175
DOI:
10.1016/j.virol.2011.02.020
[Indexed for MEDLINE]
Free PMC Article

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