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International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

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  • Wenhui Li - Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics), Harvard Medical School, Boston, Massachusetts, USA
  • Kyungwha Lee - Pulmonary Division, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
  • Sweekee Wong - Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics), Harvard Medical School, Boston, Massachusetts, USA
  • Michael Moore - Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics), Harvard Medical School, Boston, Massachusetts, USA
  • Natalya Vasilieva - Pulmonary Division, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
  • Thomas C. Greenough - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Michael Farzan - Partners AIDS Research Center, Brigham and Women's Hospital, Department of Medicine (Microbiology and Molecular Genetics), Harvard Medical School, Boston, Massachusetts, USA
  • corresponding author presenting/speaker Hyeryun Choe - Pulmonary Division, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sars12.01

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/sars2004/04sars056.shtml

Published: May 26, 2004

© 2004 Li et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Recently we identified angiotensin-converting enzyme 2 (ACE2) as a functional receptor for SARS coronavirus (SARS-CoV) [1], and showed that a 193-residue fragment of the SARS-CoV Spike (S) protein is sufficient for its high-affinity association with ACE2 [2]. Using murine leukemia virus and lentivirus pseudotyped with the SARS-CoV S protein, we demonstrated the potency of two candidate therapeutics for SARS, one based on soluble ACE2, and the other on the receptor-binding domain of the S protein [3].

Rodent orthologs of ACE2 do not support the entry of SARS-CoV efficiently, due to their low affinity for the S protein. NIH3T3 cells expressing human ACE2 allow efficient infection by SARS-CoV. These data indicate that there is no other impediment in murine cells to SARS-CoV infection, and suggest that transgenic mice expressing human ACE2 could serve as a good animal model. Also we have used differences between rodent and human ACE2 to map the S-protein-binding region of human ACE2. Differences in this region of ACE2 among various species provide some insight into the molecular determinants of the adaptation of SARS-CoV to humans.

Among a few open reading frames (ORFs) of SARS-CoV, whose function is unknown, we examined ORF7a, and identified its binding protein. The function of this target protein is under investigation.

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References

1.
Wenhui Li, Michael J. Moore, Natalya Vasilieva, Jianhua Sui, Swee Kee Wong, Michael A. Berne, Mohan Somasundaran, John L. Sullivan, Katherine Luzuriaga, Thomas C. Greenough, Hyeryun Choe, Michael Farzan. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. 2003. Nature 426 (27): 450-4
2.
Swee Kee Wong, Wenhui Li, Michael J. Moore, Hyeryun Choe, Michael Farzan. A 193-amino-acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. 2004. J Biol Chem 279(5):3197-201
3.
Michael J. Moore, Tatyana Dorfman, Wenhui Li, Swee Kee Wong, James Coderre, Natalya Vasilieva, Thomas C. Greenough, Michael Farzan, Hyeryun Choe. A lentivirus pseudotyped with the SARS-coronavirus spike protein efficiently infects ACE2-expressing cells. 2004. J Virol