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Journal of Virology, October 2004, p. 11429-11433, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11429-11433.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Efficient Replication of Severe Acute Respiratory Syndrome Coronavirus in Mouse Cells Is Limited by Murine Angiotensin-Converting Enzyme 2

Wenhui Li,1,{dagger} Thomas C. Greenough,2,{dagger} Michael J. Moore,1 Natalya Vasilieva,3 Mohan Somasundaran,2 John L. Sullivan,2 Michael Farzan,1* and Hyeryun Choe3*

Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics),1 Pulmonary Division, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston,3 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts2

Received 18 April 2004/ Accepted 8 June 2004

Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS.

* Corresponding author. Mailing address for Michael Farzan: Partners AIDS Research Center, 65 Landsdowne St., Cambridge, MA 02139. Phone: (617) 768-8372. Fax: (617) 768-8738. E-mail: farzan{at}mbcrr.harvard.edu. Mailing address for Hyeryun Choe: Pulmonary Division, Children's Hospital, 300 Longwood Ave., Boston, MA 02115. Phone: (617) 355-7586. Fax: (617) 730-0240. E-mail: hyeryun.choe{at}tch.harvard.edu.

{dagger} W.L. and T.C.G. contributed equally to this work.

Journal of Virology, October 2004, p. 11429-11433, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11429-11433.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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