Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Dec;70(12):8669–8674. doi: 10.1128/jvi.70.12.8669-8674.1996

Feline aminopeptidase N serves as a receptor for feline, canine, porcine, and human coronaviruses in serogroup I.

D B Tresnan 1, R Levis 1, K V Holmes 1
PMCID: PMC190961  PMID: 8970993

Abstract

Two members of coronavirus serogroup I, human respiratory coronavirus HCV-229E and porcine transmissible gastroenteritis virus (TGEV), use aminopeptidase N (APN) as their cellular receptors. These viruses show marked species specificity in receptor utilization, as HCV-229E can utilize human but not porcine APN, while TGEV can utilize porcine but not human APN. To determine whether feline APN could serve as a receptor for two feline coronaviruses in serogroup I, feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FeCV), we cloned the cDNA encoding feline APN (fAPN) by PCR from cDNA isolated from a feline cell line and stably expressed it in FIPV- and FeCV-resistant mouse and hamster cells. The predicted amino acid sequence of fAPN shows 78 and 77% identity with human and porcine APN, respectively. When inoculated with either of two biologically different strains of FIPV or with FeCV, fAPN-transfected mouse and hamster cells became infected and viral antigens developed in the cytoplasm. Infectious FIPV was released from hamster cells stably transfected with fAPN. The fAPN-transfected mouse and hamster cells were challenged with other coronaviruses in serogroup I including canine coronavirus, porcine coronavirus TGEV, and human coronavirus HCV-229E. In addition to serving as a receptor for the feline coronaviruses, fAPN also served as a functional receptor for each of these serogroup I coronaviruses as shown by development of viral antigens in the cytoplasm of infected mouse or hamster cells stably transfected with fAPN. In contrast, fAPN did not serve as a functional receptor for mouse hepatitis virus (MHV-A59), which is in serogroup II and utilizes mouse biliary glycoprotein receptors unrelated to APN. Thus, fAPN serves as a receptor for a much broader range of group I coronaviruses than human and porcine APNs. The human, porcine, and canine coronaviruses in serogroup I that are able to use fAPN as a receptor have previously been shown to infect cats without causing disease. Therefore, host factors in addition to receptor specificity apparently affect the virulence and transmissibility of nonfeline serogroup I coronaviruses in the cat.

Full Text

The Full Text of this article is available as a PDF (272.0 KB).

Selected References

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

  1. Barlough J. E., Johnson-Lussenburg C. M., Stoddart C. A., Jacobson R. H., Scott F. W. Experimental inoculation of cats with human coronavirus 229E and subsequent challenge with feline infectious peritonitis virus. Can J Comp Med. 1985 Jul;49(3):303–307. [PMC free article] [PubMed] [Google Scholar]
  2. Barlough J. E., Stoddart C. A., Sorresso G. P., Jacobson R. H., Scott F. W. Experimental inoculation of cats with canine coronavirus and subsequent challenge with feline infectious peritonitis virus. Lab Anim Sci. 1984 Dec;34(6):592–597. [PubMed] [Google Scholar]
  3. Boyle J. F., Pedersen N. C., Evermann J. F., McKeirnan A. J., Ott R. L., Black J. W. Plaque assay, polypeptide composition and immunochemistry of feline infectious peritonitis virus and feline enteric coronavirus isolates. Adv Exp Med Biol. 1984;173:133–147. doi: 10.1007/978-1-4615-9373-7_12. [DOI] [PubMed] [Google Scholar]
  4. Castrucci M. R., Donatelli I., Sidoli L., Barigazzi G., Kawaoka Y., Webster R. G. Genetic reassortment between avian and human influenza A viruses in Italian pigs. Virology. 1993 Mar;193(1):503–506. doi: 10.1006/viro.1993.1155. [DOI] [PubMed] [Google Scholar]
  5. Compton S. R., Stephensen C. B., Snyder S. W., Weismiller D. G., Holmes K. V. Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein. J Virol. 1992 Dec;66(12):7420–7428. doi: 10.1128/jvi.66.12.7420-7428.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delmas B., Gelfi J., Kut E., Sjöström H., Noren O., Laude H. Determinants essential for the transmissible gastroenteritis virus-receptor interaction reside within a domain of aminopeptidase-N that is distinct from the enzymatic site. J Virol. 1994 Aug;68(8):5216–5224. doi: 10.1128/jvi.68.8.5216-5224.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Dveksler G. S., Dieffenbach C. W., Cardellichio C. B., McCuaig K., Pensiero M. N., Jiang G. S., Beauchemin N., Holmes K. V. Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol. 1993 Jan;67(1):1–8. doi: 10.1128/jvi.67.1.1-8.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dveksler G. S., Pensiero M. N., Cardellichio C. B., Williams R. K., Jiang G. S., Holmes K. V., Dieffenbach C. W. Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. J Virol. 1991 Dec;65(12):6881–6891. doi: 10.1128/jvi.65.12.6881-6891.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
  12. Keck J. G., Makino S., Soe L. H., Fleming J. O., Stohlman S. A., Lai M. M. RNA recombination of coronavirus. Adv Exp Med Biol. 1987;218:99–107. doi: 10.1007/978-1-4684-1280-2_11. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Levis R., Cardellichio C. B., Scanga C. A., Compton S. R., Holmes K. V. Multiple receptor-dependent steps determine the species specificity of HCV-229E infection. Adv Exp Med Biol. 1995;380:337–343. doi: 10.1007/978-1-4615-1899-0_55. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Makino S., Keck J. G., Stohlman S. A., Lai M. M. High-frequency RNA recombination of murine coronaviruses. J Virol. 1986 Mar;57(3):729–737. doi: 10.1128/jvi.57.3.729-737.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Montali R. J., Strandberg J. D. Extraperitoneal lesions in feline infectious peritonitis. Vet Pathol. 1972;9(2):109–121. doi: 10.1177/030098587200900204. [DOI] [PubMed] [Google Scholar]
  18. O'Brien S. J., Roelke M. E., Marker L., Newman A., Winkler C. A., Meltzer D., Colly L., Evermann J. F., Bush M., Wildt D. E. Genetic basis for species vulnerability in the cheetah. Science. 1985 Mar 22;227(4693):1428–1434. doi: 10.1126/science.2983425. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Pedersen N. C., Boyle J. F., Floyd K., Fudge A., Barker J. An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. Am J Vet Res. 1981 Mar;42(3):368–377. [PubMed] [Google Scholar]
  21. Pedersen N. C. Morphologic and physical characteristics of feline infectious peritonitis virus and its growth in autochthonous peritoneal cell cultures. Am J Vet Res. 1976 May;37(5):567–572. [PubMed] [Google Scholar]
  22. Pedersen N. C. Virologic and immunologic aspects of feline infectious peritonitis virus infection. Adv Exp Med Biol. 1987;218:529–550. doi: 10.1007/978-1-4684-1280-2_69. [DOI] [PubMed] [Google Scholar]
  23. Petersen N. C., Boyle J. F. Immunologic phenomena in the effusive form of feline infectious peritonitis. Am J Vet Res. 1980 Jun;41(6):868–876. [PubMed] [Google Scholar]
  24. Pfeifer M. L., Evermann J. F., Roelke M. E., Gallina A. M., Ott R. L., McKeirnan A. J. Feline infectious peritonitis in a captive cheetah. J Am Vet Med Assoc. 1983 Dec 1;183(11):1317–1319. [PubMed] [Google Scholar]
  25. Reynolds D. J., Garwes D. J. Virus isolation and serum antibody responses after infection of cats with transmissible gastroenteritis virus. Brief report. Arch Virol. 1979;60(2):161–166. doi: 10.1007/BF01348032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schultze B., Gross H. J., Brossmer R., Herrler G. The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant. J Virol. 1991 Nov;65(11):6232–6237. doi: 10.1128/jvi.65.11.6232-6237.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schultze B., Herrler G. Bovine coronavirus uses N-acetyl-9-O-acetylneuraminic acid as a receptor determinant to initiate the infection of cultured cells. J Gen Virol. 1992 Apr;73(Pt 4):901–906. doi: 10.1099/0022-1317-73-4-901. [DOI] [PubMed] [Google Scholar]
  29. Scott F. W. Immunization against feline coronaviruses. Adv Exp Med Biol. 1987;218:569–576. doi: 10.1007/978-1-4684-1280-2_72. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Siddell S., Wege H., Ter Meulen V. The biology of coronaviruses. J Gen Virol. 1983 Apr;64(Pt 4):761–776. doi: 10.1099/0022-1317-64-4-761. [DOI] [PubMed] [Google Scholar]
  32. Stoddart C. A., Scott F. W. Intrinsic resistance of feline peritoneal macrophages to coronavirus infection correlates with in vivo virulence. J Virol. 1989 Jan;63(1):436–440. doi: 10.1128/jvi.63.1.436-440.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Watt V. M., Yip C. C. Amino acid sequence deduced from a rat kidney cDNA suggests it encodes the Zn-peptidase aminopeptidase N. J Biol Chem. 1989 Apr 5;264(10):5480–5487. [PubMed] [Google Scholar]
  34. Webster R. G., Laver W. G., Air G. M., Schild G. C. Molecular mechanisms of variation in influenza viruses. Nature. 1982 Mar 11;296(5853):115–121. doi: 10.1038/296115a0. [DOI] [PubMed] [Google Scholar]
  35. Wege H., Siddell S., ter Meulen V. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol. 1982;99:165–200. doi: 10.1007/978-3-642-68528-6_5. [DOI] [PubMed] [Google Scholar]
  36. Woods R. D., Cheville N. F., Gallagher J. E. Lesions in the small intestine of newborn pigs inoculated with porcine, feline, and canine coronaviruses. Am J Vet Res. 1981 Jul;42(7):1163–1169. [PubMed] [Google Scholar]
  37. Yang X. F., Milhiet P. E., Gaudoux F., Crine P., Boileau G. Complete sequence of rabbit kidney aminopeptidase N and mRNA localization in rabbit kidney by in situ hybridization. Biochem Cell Biol. 1993 May-Jun;71(5-6):278–287. doi: 10.1139/o93-042. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Yokomori K., Lai M. M. Mouse hepatitis virus utilizes two carcinoembryonic antigens as alternative receptors. J Virol. 1992 Oct;66(10):6194–6199. doi: 10.1128/jvi.66.10.6194-6199.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES