Article
- The EMBO Journal (2005) 24, 1634 - 1643
- doi:10.1038/sj.emboj.7600640
Published online: 24 March 2005
Subject Categories:
Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2
Wenhui Li1, Chengsheng Zhang2,3, Jianhua Sui4, Jens H Kuhn1,5, Michael J Moore1, Shiwen Luo3, Swee-Kee Wong1, I-Chueh Huang1, Keming Xu3, Natalya Vasilieva6, Akikazu Murakami4, Yaqing He7, Wayne A Marasco4, Yi Guan3, Hyeryun Choe6 and Michael Farzan1
- Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA, USA
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, PRC
- Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Berlin, Germany
- Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA, USA
- Center for Disease Control and Prevention of Shenzhen, Shenzhen, Guangdong Province, PRC
Correspondence to:
Yi Guan, Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, PRC. E-mail: yguan@hkucc.hku.hk
Hyeryun Choe, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. E-mail: hyeryun.choe@tch.harvard.edu
Michael Farzan, Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772-9102, USA. Tel.: +1 617 768 8372; Fax: +1 617 768 8738; E-mail: farzan@hms.harvard.edu
Received 9 December 2004; Accepted 4 March 2005
Abstract
Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.
Keywords:
- angiotensin-converting enzyme 2,
- coronavirus,
- severe acute respiratory syndrome,
- viral adaptation
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