Abstract
HUMAN coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43 are an important cause of upper respiratory tract infections1. Here we report that human aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and kidney epithelial cells2–5, is a receptor for human coronavirus strain HCV-229E, but not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus infection of human lung fibroblasts, immunoprecipitated aminopeptidase N and inhibited its enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible after transfection with complementary DNA encoding human aminopeptidase N. By contrast, infection of human cells with HCV-OC43 was not inhibited by antibody RBS and expression of aminopeptidase N did not enhance HCV-OC43 replication in mouse cells. A mutant aminopeptidase lacking the catalytic site of the enzyme did not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E infection, suggesting that the virus-binding site may lie at or near the active site of the human aminopeptidase molecule.
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Mclntosh, K. in Virology 2nd edn (eds Fields, D. N. et al.) 857–864 (Raven, New York, 1990).
Noren, O., Sjostrom, H., Danielsen, E. M., Cowell, G. M. & Skovbjerg, H. in Molecular and Cellular Basis of Digestion (ed. Desnuelle, P.) 335–363 (Elsevier, Amsterdam, 1986).
Semenza, G. A. Rev. Cell Biol. 2, 255–313 (1986).
Kenny, A. J. & Maroux, S. Physiol. Rev. 62, 91–128 (1982).
Matsas, R., Stephenson, S. L., Hryszko, J., Kenny, A. J. & Turnover, A. J. Biochem. J. 231, 445–449 (1985).
Sakaguchi, A. Y. & Shows, T. B. Somatic Cell Genet. 8, 83–94 (1982).
Look, A. T. et al. J. clin. Invest. 78, 914–921 (1986).
Turner, A. J., Hooper, N. M. & Kenny, A. J. in Mammalian Ectoenzymes (eds Kenny, A. J. & Turner, A. J.) 211–248 (Elsevier, Amsterdam, 1987).
Look, A. T., Ashmun, R. A., Shapiro, L. H. & Peiper, S. C. J. clin. Invest. 83, 1299–1307 (1989).
Look, A. T. et al. in Leukocyte Typing IV (eds Knapp, W. et al.) 784–787 (Oxford Univ. Press. Oxford, 1989).
Delmas, B. et al. Nature 357, 417–420 (1992).
Olsen, J., Sjostrom, H. & Noren, O. FEBS Lett. 251, 275–81 (1989).
Noren, O. et al. FEBS Lett. 259, 107–112 (1989).
Watt, V. M. & Yip, C. C. J. biol. Chem. 264, 5480–5487 (1989).
Ashmun, R. A. & Look, A. T. Blood 75, 462–469 (1990).
Look, A. T. et al. J. clin. Invest. 75, 569–579 (1985).
Ashmun, R. A., Shapiro, L. H. & Look, A. T. Blood (in the press).
Vallee, B. L. & Auld, D. S. Biochemistry 29, 5647–5659 (1990).
Umezawa, H. et al. J. Antibiotics 38, 1629–1630 (1985).
Rich, D. H., Moon, B. J. & Harbeson, S. J. med. Chem. 27, 417–422 (1984).
Wilkes, S. H. & Prescott, J. M. J. biol. Chem. 260, 13154–13162 (1985).
Williams, R. K., Jiang, G. S., Snyder, S. W., Frana, M. F. & Holmes, K. V. J. Virol. 64, 3817–3823 (1990).
Williams, R. K., Jiang, G. S. & Holmes, K. V. Proc. natn. Acad. Sci. U.S.A. 88, 5533–5536 (1990).
Dveksler, G. S. et al. J. Virol. 65, 8881–6891 (1991).
Wu, Q., Lahti, J. M., Air, G. M., Burrows, P. D. & Cooper, M. D. Proc. natn. Acad. Sci. U.S.A. 87, 993–997 (1990).
Wu, Q., Li, L., Cooper, M. D., Pierres, M. & Gorvel, J. P. Proc. natn. Acad. Sci. U.S.A. 88, 676–680 (1991).
Devault, A. et al. EMBO J. 6, 1317–1322 (1987).
Malfroy, B., Kuang, W.-J., Seeburg, P. H., Mason, A. J. & Schofield, P. R. FEBS Lett. 229, 206–210 (1988).
Letarte, M. et al. J. exp. Med. 168, 1247–1253 (1988).
Shipp, M. A. et al. Proc. natn. Acad. Sci. U.S.A. 86, 297–301 (1989).
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Yeager, C., Ashmun, R., Williams, R. et al. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 357, 420–422 (1992). https://doi.org/10.1038/357420a0
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DOI: https://doi.org/10.1038/357420a0
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