JVI Accepts, published online ahead of print on 28 October 2009

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J. Virol. doi:10.1128/JVI.01248-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Differential downregulation of ACE2 by the spike proteins of SARS-coronavirus and human coronavirus NL63

Ilona Glowacka, Stephanie Bertram, Petra Herzog, Susanne Pfefferle, Imke Steffen, Marcus O. Muench, Graham Simmons, Heike Hofmann, Thomas Kuri, Friedemann Weber, Jutta Eichler, Christian Drosten, and Stefan Pöhlmann^*

Institute of Virology, Hannover Medical School, 30625 Hannover, Germany; and Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany; and Qiagen Hamburg GmbH, Königstr. 4a, D-22767 Hamburg, Germany; and Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, CA, USA; and Department of Medical Microbiology and Virology, University of Kiel, 24105 Kiel, Germany; and Department of Virology, University of Freiburg, D-79008 Freiburg, Germany; and Department Medicinal Chemistry, University of Erlangen-Nürnberg, Schuhstrasse 19, 91052 Erlangen, Germany; and Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-St. 25, 53127 Bonn, Germany

^* To whom correspondence should be addressed. Email: Poehlmann.Stefan{at}MH-Hannover.DE.

The human coronaviruses (CoVs) SARS-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV-spike (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 downregulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.