Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Human aminopeptidase N is a receptor for human coronavirus 229E

Nature volume 357, pages 420–422 (1992)Cite this article

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.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Mclntosh, K. in Virology 2nd edn (eds Fields, D. N. et al.) 857–864 (Raven, New York, 1990).

    Google Scholar 

  2. 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).

    Google Scholar 

  3. Semenza, G. A. Rev. Cell Biol. 2, 255–313 (1986).

    Article  CAS  Google Scholar 

  4. Kenny, A. J. & Maroux, S. Physiol. Rev. 62, 91–128 (1982).

    Article  CAS  Google Scholar 

  5. Matsas, R., Stephenson, S. L., Hryszko, J., Kenny, A. J. & Turnover, A. J. Biochem. J. 231, 445–449 (1985).

    Article  CAS  Google Scholar 

  6. Sakaguchi, A. Y. & Shows, T. B. Somatic Cell Genet. 8, 83–94 (1982).

    Article  CAS  Google Scholar 

  7. Look, A. T. et al. J. clin. Invest. 78, 914–921 (1986).

    Article  CAS  Google Scholar 

  8. Turner, A. J., Hooper, N. M. & Kenny, A. J. in Mammalian Ectoenzymes (eds Kenny, A. J. & Turner, A. J.) 211–248 (Elsevier, Amsterdam, 1987).

    Google Scholar 

  9. Look, A. T., Ashmun, R. A., Shapiro, L. H. & Peiper, S. C. J. clin. Invest. 83, 1299–1307 (1989).

    Article  CAS  Google Scholar 

  10. Look, A. T. et al. in Leukocyte Typing IV (eds Knapp, W. et al.) 784–787 (Oxford Univ. Press. Oxford, 1989).

    Google Scholar 

  11. Delmas, B. et al. Nature 357, 417–420 (1992).

    Article  ADS  CAS  Google Scholar 

  12. Olsen, J., Sjostrom, H. & Noren, O. FEBS Lett. 251, 275–81 (1989).

    Article  CAS  Google Scholar 

  13. Noren, O. et al. FEBS Lett. 259, 107–112 (1989).

    Article  CAS  Google Scholar 

  14. Watt, V. M. & Yip, C. C. J. biol. Chem. 264, 5480–5487 (1989).

    CAS  PubMed  Google Scholar 

  15. Ashmun, R. A. & Look, A. T. Blood 75, 462–469 (1990).

    CAS  PubMed  Google Scholar 

  16. Look, A. T. et al. J. clin. Invest. 75, 569–579 (1985).

    Article  CAS  Google Scholar 

  17. Ashmun, R. A., Shapiro, L. H. & Look, A. T. Blood (in the press).

  18. Vallee, B. L. & Auld, D. S. Biochemistry 29, 5647–5659 (1990).

    Article  CAS  Google Scholar 

  19. Umezawa, H. et al. J. Antibiotics 38, 1629–1630 (1985).

    Article  CAS  Google Scholar 

  20. Rich, D. H., Moon, B. J. & Harbeson, S. J. med. Chem. 27, 417–422 (1984).

    Article  CAS  Google Scholar 

  21. Wilkes, S. H. & Prescott, J. M. J. biol. Chem. 260, 13154–13162 (1985).

    CAS  PubMed  Google Scholar 

  22. Williams, R. K., Jiang, G. S., Snyder, S. W., Frana, M. F. & Holmes, K. V. J. Virol. 64, 3817–3823 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Williams, R. K., Jiang, G. S. & Holmes, K. V. Proc. natn. Acad. Sci. U.S.A. 88, 5533–5536 (1990).

    Article  ADS  Google Scholar 

  24. Dveksler, G. S. et al. J. Virol. 65, 8881–6891 (1991).

    Google Scholar 

  25. 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).

    Article  ADS  CAS  Google Scholar 

  26. Wu, Q., Li, L., Cooper, M. D., Pierres, M. & Gorvel, J. P. Proc. natn. Acad. Sci. U.S.A. 88, 676–680 (1991).

    Article  ADS  CAS  Google Scholar 

  27. Devault, A. et al. EMBO J. 6, 1317–1322 (1987).

    Article  CAS  Google Scholar 

  28. Malfroy, B., Kuang, W.-J., Seeburg, P. H., Mason, A. J. & Schofield, P. R. FEBS Lett. 229, 206–210 (1988).

    Article  CAS  Google Scholar 

  29. Letarte, M. et al. J. exp. Med. 168, 1247–1253 (1988).

    Article  CAS  Google Scholar 

  30. Shipp, M. A. et al. Proc. natn. Acad. Sci. U.S.A. 86, 297–301 (1989).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Kathryn V. Holmes: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, 20814-4799, USA

    Curtis L. Yeager, Richard K. Williams, Christine B. Cardellichio & Kathryn V. Holmes

  2. Department of Hematology/Oncology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Richard A. Ashmun, Linda H. Shapiro & A. Thomas Look

  3. Department of Tumor Cell Biology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38105, USA

    Richard A. Ashmun & A. Thomas Look

  4. Department of Pediatrics, University of Tennessee College of Medicine, Memphis, Tennessee, 38163, USA

    A. Thomas Look

Authors
  1. Curtis L. Yeager
    View author publications

    Search author on:PubMed Google Scholar

  2. Richard A. Ashmun
    View author publications

    Search author on:PubMed Google Scholar

  3. Richard K. Williams
    View author publications

    Search author on:PubMed Google Scholar

  4. Christine B. Cardellichio
    View author publications

    Search author on:PubMed Google Scholar

  5. Linda H. Shapiro
    View author publications

    Search author on:PubMed Google Scholar

  6. A. Thomas Look
    View author publications

    Search author on:PubMed Google Scholar

  7. Kathryn V. Holmes
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1038/357420a0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing