Angiotensin-I converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV). A previous study indicated that ACE2 from a horseshoe bat, the host of a highly related SARS-like coronavirus, could not function as a receptor for SARS-CoV. Here, we demonstrate that a 3 aa change from SHE (aa 40–42) to FYQ was sufficient to convert the bat ACE2 into a fully functional receptor for SARS-CoV. We further demonstrate that an ACE2 molecule from a fruit bat, which contains the FYQ motif, was able to support SARS-CoV infection, indicating a potentially much wider host range for SARS-CoV-related viruses among different bat populations.


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  1. Drosten, C., Gunther, S., Preiser, W., Van Der Werf, S., Brodt, H. R., Becker, S., Rabenau, H., Panning, M., Kolesnikova, L. & other authors(2003). Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348, 1967–1976.[CrossRef] [Google Scholar]
  2. Flanders, J., Jones, G., Benda, P., Dietz, C., Zhang, S., Li, G., Sharifi, M. & Rossiter, S. J.(2009). Phylogeography of the greater horseshoe bat, Rhinolophus ferrumequinum: contrasting results from mitochondrial and microsatellite data. Mol Ecol 18, 306–318.[CrossRef] [Google Scholar]
  3. Guan, Y., Zheng, B. J., He, Y. Q., Liu, X. L., Zhuang, Z. X., Cheung, C. L., Luo, S. W., Li, P. H., Zhang, L. J. & other authors(2003). Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302, 276–278.[CrossRef] [Google Scholar]
  4. Han, D. P., Penn-Nicholson, A. & Cho, M. W.(2006). Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor. Virology 350, 15–25.[CrossRef] [Google Scholar]
  5. Ksiazek, T. G., Erdman, D., Goldsmith, C. S., Zaki, S. R., Peret, T., Emery, S., Tong, S., Urbani, C., Comer, J. A. & other authors(2003). A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348, 1953–1966.[CrossRef] [Google Scholar]
  6. Kuba, K., Imai, Y., Rao, S., Jiang, C. & Penninger, J. M.(2006). Lessons from SARS: control of acute lung failure by the SARS receptor ACE2. J Mol Med 84, 814–820.[CrossRef] [Google Scholar]
  7. Kuhn, J. H., Li, W., Radoshitzky, S. R., Choe, H. & Farzan, M.(2007). Severe acute respiratory syndrome coronavirus entry as a target of antiviral therapies. Antivir Ther 12, 639–650. [Google Scholar]
  8. Lau, S. K., Woo, P. C., Li, K. S., Huang, Y., Tsoi, H. W., Wong, B. H., Wong, S. S., Leung, S. Y., Chan, K. H. & other authors(2005). Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc Natl Acad Sci U S A 102, 14040–14045.[CrossRef] [Google Scholar]
  9. Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K. & other authors(2003). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450–454.[CrossRef] [Google Scholar]
  10. Li, F., Li, W., Farzan, M. & Harrison, S. C.(2005a). Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309, 1864–1868.[CrossRef] [Google Scholar]
  11. Li, W., Shi, Z., Yu, M., Ren, W., Smith, C., Epstein, J. H., Wang, H., Crameri, G., Hu, Z. & other authors(2005b). Bats are natural reservoirs of SARS-like coronaviruses. Science 310, 676–679.[CrossRef] [Google Scholar]
  12. Li, W., Wong, S. K., Li, F., Kuhn, J. H., Huang, I. C., Choe, H. & Farzan, M.(2006). Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions. J Virol 80, 4211–4219.[CrossRef] [Google Scholar]
  13. Normile, D. & Enserink, M.(2003). SARS in China. Tracking the roots of a killer. Science 301, 297–299.[CrossRef] [Google Scholar]
  14. Peiris, J. S.(2003). Severe acute respiratory syndrome (SARS). J Clin Virol 28, 245–247.[CrossRef] [Google Scholar]
  15. Peiris, J. S., Lai, S. T., Poon, L. L., Guan, Y., Yam, L. Y., Lim, W., Nicholls, J., Yee, W. K., Yan, W. W. & other authors(2003). Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361, 1319–1325.[CrossRef] [Google Scholar]
  16. Peiris, J. S., Guan, Y. & Yuen, K. Y.(2004). Severe acute respiratory syndrome. Nat Med 10, S88–S97.[CrossRef] [Google Scholar]
  17. Ren, W., Qu, X., Li, W., Han, Z., Yu, M., Zhou, P., Zhang, S. Y., Wang, L. F., Deng, H. & other authors(2008). Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. J Virol 82, 1899–1907.[CrossRef] [Google Scholar]
  18. Rossiter, S. J., Benda, P., Dietz, C., Zhang, S. & Jones, G.(2007). Rangewide phylogeography in the greater horseshoe bat inferred from microsatellites: implications for population history, taxonomy and conservation. Mol Ecol 16, 4699–4714.[CrossRef] [Google Scholar]
  19. Sheahan, T., Rockx, B., Donaldson, E., Sims, A., Pickles, R., Corti, D. & Baric, R.(2008). Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium. J Virol 82, 2274–2285.[CrossRef] [Google Scholar]
  20. Tu, C., Crameri, G., Kong, X., Chen, J., Sun, Y., Yu, M., Xiang, H., Xia, X., Liu, S. & other authors(2004). Antibodies to SARS coronavirus in civets. Emerg Infect Dis 10, 2244–2248.[CrossRef] [Google Scholar]
  21. Wang, L. F. & Eaton, B. T.(2007). Bats, civets and the emergence of SARS. Curr Top Microbiol Immunol 315, 325–344. [Google Scholar]
  22. Wang, L., Hertzog, P. J., Galanis, M., Overall, M. L., Waine, G. J. & Linnane, A. W.(1994). Structure-function analysis of human IFN-alpha. Mapping of a conformational epitope by homologue scanning. J Immunol 152, 705–715. [Google Scholar]
  23. Wang, L. F., Shi, Z., Zhang, S., Field, H., Daszak, P. & Eaton, B. T.(2006). Review of bats and SARS. Emerg Infect Dis 12, 1834–1840.[CrossRef] [Google Scholar]
  24. Yu, M., Stevens, V., Berry, J. D., Crameri, G., McEachern, J., Tu, C., Shi, Z., Liang, G., Weingartl, H. & other authors(2008). Determination and application of immunodominant regions of SARS coronavirus spike and nucleocapsid proteins recognized by sera from different animal species. J Immunol Methods 331, 1–12.[CrossRef] [Google Scholar]

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