Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Aug;68(8):5216–5224. doi: 10.1128/jvi.68.8.5216-5224.1994

Determinants essential for the transmissible gastroenteritis virus-receptor interaction reside within a domain of aminopeptidase-N that is distinct from the enzymatic site.

B Delmas 1, J Gelfi 1, E Kut 1, H Sjöström 1, O Noren 1, H Laude 1
PMCID: PMC236465  PMID: 7913510

Abstract

The swine-specific coronavirus transmissible gastroenteritis virus (TGEV) uses pig aminopeptidase-N (pAPN) as a cellular receptor. We showed that the human aminopeptidase-N (hAPN) cannot substitute for pAPN in this respect, although the two enzymes have 80% amino acid sequence identity. In order to map the TGEV binding site on pAPN, we constructed a series of APN cDNA chimeras between pAPN and hAPN and analyzed them for their capacity to confer infectivity. The region between residues 717 and 813 was found to be essential for infectivity. This region also contains the epitopes for three TGEV-blocking monoclonal antibodies directed against pAPN. These data support the view that the catalytic site and the TGEV receptor site are located in different domains. Moreover, APN inhibitors and mutations in the catalytic site had no obvious effect on permissiveness for virus, thus providing evidence that the APN enzymatic activity is not involved in the process of infection.

Full text

PDF
5216

Images in this article

5223Image
on p.5223

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashmun R. A., Shapiro L. H., Look A. T. Deletion of the zinc-binding motif of CD13/aminopeptidase N molecules results in loss of epitopes that mediate binding of inhibitory antibodies. Blood. 1992 Jun 15;79(12):3344–3349. [PubMed] [Google Scholar]
  2. Callebaut C., Krust B., Jacotot E., Hovanessian A. G. T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells. Science. 1993 Dec 24;262(5142):2045–2050. doi: 10.1126/science.7903479. [DOI] [PubMed] [Google Scholar]
  3. Delmas B., Gelfi J., L'Haridon R., Vogel L. K., Sjöström H., Norén O., Laude H. Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature. 1992 Jun 4;357(6377):417–420. doi: 10.1038/357417a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Delmas B., Gelfi J., Sjöström H., Noren O., Laude H. Further characterization of aminopeptidase-N as a receptor for coronaviruses. Adv Exp Med Biol. 1993;342:293–298. doi: 10.1007/978-1-4615-2996-5_45. [DOI] [PubMed] [Google Scholar]
  5. Devault A., Sales V., Nault C., Beaumont A., Roques B., Crine P., Boileau G. Exploration of the catalytic site of endopeptidase 24.11 by site-directed mutagenesis. Histidine residues 583 and 587 are essential for catalysis. FEBS Lett. 1988 Apr 11;231(1):54–58. doi: 10.1016/0014-5793(88)80701-4. [DOI] [PubMed] [Google Scholar]
  6. Duarte M., Gelfi J., Lambert P., Rasschaert D., Laude H. Genome organization of porcine epidemic diarrhoea virus. Adv Exp Med Biol. 1993;342:55–60. doi: 10.1007/978-1-4615-2996-5_9. [DOI] [PubMed] [Google Scholar]
  7. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. doi: 10.1016/0378-1119(89)90358-2. [DOI] [PubMed] [Google Scholar]
  8. Johansen T. E., Schøller M. S., Tolstoy S., Schwartz T. W. Biosynthesis of peptide precursors and protease inhibitors using new constitutive and inducible eukaryotic expression vectors. FEBS Lett. 1990 Jul 16;267(2):289–294. doi: 10.1016/0014-5793(90)80947-h. [DOI] [PubMed] [Google Scholar]
  9. Jongeneel C. V., Bouvier J., Bairoch A. A unique signature identifies a family of zinc-dependent metallopeptidases. FEBS Lett. 1989 Jan 2;242(2):211–214. doi: 10.1016/0014-5793(89)80471-5. [DOI] [PubMed] [Google Scholar]
  10. Kenny A. J., Maroux S. Topology of microvillar membrance hydrolases of kidney and intestine. Physiol Rev. 1982 Jan;62(1):91–128. doi: 10.1152/physrev.1982.62.1.91. [DOI] [PubMed] [Google Scholar]
  11. Kueng W., Silber E., Eppenberger U. Quantification of cells cultured on 96-well plates. Anal Biochem. 1989 Oct;182(1):16–19. doi: 10.1016/0003-2697(89)90710-0. [DOI] [PubMed] [Google Scholar]
  12. Landau N. R., Warton M., Littman D. R. The envelope glycoprotein of the human immunodeficiency virus binds to the immunoglobulin-like domain of CD4. Nature. 1988 Jul 14;334(6178):159–162. doi: 10.1038/334159a0. [DOI] [PubMed] [Google Scholar]
  13. Laude H., Chapsal J. M., Gelfi J., Labiau S., Grosclaude J. Antigenic structure of transmissible gastroenteritis virus. I. Properties of monoclonal antibodies directed against virion proteins. J Gen Virol. 1986 Jan;67(Pt 1):119–130. doi: 10.1099/0022-1317-67-1-119. [DOI] [PubMed] [Google Scholar]
  14. Look A. T., Ashmun R. A., Shapiro L. H., Peiper S. C. Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. J Clin Invest. 1989 Apr;83(4):1299–1307. doi: 10.1172/JCI114015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McClelland A., deBear J., Yost S. C., Meyer A. M., Marlor C. W., Greve J. M. Identification of monoclonal antibody epitopes and critical residues for rhinovirus binding in domain 1 of intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7993–7997. doi: 10.1073/pnas.88.18.7993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morrison M. E., Racaniello V. R. Molecular cloning and expression of a murine homolog of the human poliovirus receptor gene. J Virol. 1992 May;66(5):2807–2813. doi: 10.1128/jvi.66.5.2807-2813.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Olsen J., Cowell G. M., Kønigshøfer E., Danielsen E. M., Møller J., Laustsen L., Hansen O. C., Welinder K. G., Engberg J., Hunziker W. Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA. FEBS Lett. 1988 Oct 10;238(2):307–314. doi: 10.1016/0014-5793(88)80502-7. [DOI] [PubMed] [Google Scholar]
  18. Olsen J., Sjöström H., Norén O. Cloning of the pig aminopeptidase N gene. Identification of possible regulatory elements and the exon distribution in relation to the membrane-spanning region. FEBS Lett. 1989 Jul 17;251(1-2):275–281. doi: 10.1016/0014-5793(89)81470-x. [DOI] [PubMed] [Google Scholar]
  19. Semenza G. Anchoring and biosynthesis of stalked brush border membrane proteins: glycosidases and peptidases of enterocytes and renal tubuli. Annu Rev Cell Biol. 1986;2:255–313. doi: 10.1146/annurev.cb.02.110186.001351. [DOI] [PubMed] [Google Scholar]
  20. Staunton D. E., Dustin M. L., Erickson H. P., Springer T. A. The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus. Cell. 1990 Apr 20;61(2):243–254. doi: 10.1016/0092-8674(90)90805-o. [DOI] [PubMed] [Google Scholar]
  21. Söderberg C., Giugni T. D., Zaia J. A., Larsson S., Wahlberg J. M., Möller E. CD13 (human aminopeptidase N) mediates human cytomegalovirus infection. J Virol. 1993 Nov;67(11):6576–6585. doi: 10.1128/jvi.67.11.6576-6585.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Webster R. G., Rott R. Influenza virus A pathogenicity: the pivotal role of hemagglutinin. Cell. 1987 Aug 28;50(5):665–666. doi: 10.1016/0092-8674(87)90321-7. [DOI] [PubMed] [Google Scholar]
  23. Wessels H. P., Hansen G. H., Fuhrer C., Look A. T., Sjöström H., Norén O., Spiess M. Aminopeptidase N is directly sorted to the apical domain in MDCK cells. J Cell Biol. 1990 Dec;111(6 Pt 2):2923–2930. doi: 10.1083/jcb.111.6.2923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yeager C. L., Ashmun R. A., Williams R. K., Cardellichio C. B., Shapiro L. H., Look A. T., Holmes K. V. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992 Jun 4;357(6377):420–422. doi: 10.1038/357420a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yokomori K., Asanaka M., Stohlman S. A., Lai M. M. A spike protein-dependent cellular factor other than the viral receptor is required for mouse hepatitis virus entry. Virology. 1993 Sep;196(1):45–56. doi: 10.1006/viro.1993.1453. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES