1887

Abstract

Porcine epidemic diarrhea virus (PEDV), a causative agent of pig diarrhoea, has recently caused significant economic damage worldwide. Porcine aminopeptidase N (pAPN) has been reported to be the receptor for PEDV, although robust evidence is lacking. In the present study, we explored whether pAPN functions as a receptor for PEDV. Human HeLa cells expressing pAPN and pAPN-positive porcine CPK cells failed to support PEDV infection, but were susceptible to infection by transmissible gastroenteritis virus (TGEV), which utilizes pAPN as a functional receptor. In contrast to TGEV, PEDV did not bind soluble porcine aminopeptidases (pAPs) and infection was not inhibited by the soluble form of pAPs. However, overexpression of pAPN in porcine CPK cells (CPK-pAPN cells) slightly increased the production of PEDV, and the increased replication in CPK-pAPN cells was inhibited by bestatin, an inhibitor of the protease activity of aminopeptidase N. These results suggest that pAPN is not a functional receptor for PEDV, but promotes the infection of PEDV through its protease activity.

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2016-10-13
2019-10-15
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References

  1. Balliet J. W., Berson J., D'Cruz C. M., Huang J., Crane J., Gilbert J. M., Bates P..( 1999;). Production and characterization of a soluble, active form of Tva, the subgroup a avian sarcoma and leukosis virus receptor. . J Virol 73: 3054–3061.[PubMed]
    [Google Scholar]
  2. Breslin J. J., Mørk I., Smith M. K., Vogel L. K., Hemmila E. M., Bonavia A., Talbot P. J., Sjöström H., Norén O., Holmes K. V..( 2003;). Human coronavirus 229E: receptor binding domain and neutralization by soluble receptor at 37 degrees C. . J Virol 77: 4435–4438. [CrossRef] [PubMed]
    [Google Scholar]
  3. Chasey D., Cartwright S. F..( 1978;). Virus-like particles associated with porcine epidemic diarrhoea. . Res Vet Sci 25: 255–256.[PubMed]
    [Google Scholar]
  4. Chen J. F., Sun D. B., Wang C. B., Shi H. Y., Cui X. C., Liu S. W., Qiu H. J., Feng L..( 2008;). Molecular characterization and phylogenetic analysis of membrane protein genes of porcine epidemic diarrhea virus isolates in China. . Virus Genes 36: 355–364. [CrossRef] [PubMed]
    [Google Scholar]
  5. Chen L., Lin Y. L., Peng G., Li F..( 2012;). Structural basis for multifunctional roles of mammalian aminopeptidase N. . Proc Natl Acad Sci U S A 109: 17966–17971. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chen Q., Li G., Stasko J., Thomas J. T., Stensland W. R., Pillatzki A. E., Gauger P. C., Schwartz K. J., Madson D. et al.( 2014;). Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States. . J Clin Microbiol 52: 234–243. [CrossRef] [PubMed]
    [Google Scholar]
  7. Cong Y., Li X., Bai Y., Lv X., Herrler G., Enjuanes L., Zhou X., Qu B., Meng F. et al.( 2015;). Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells. . Virology 478: 1–8. [CrossRef] [PubMed]
    [Google Scholar]
  8. Delmas B., Gelfi J., L'Haridon R., Vogel L. K., Sjöström H., Norén O., Laude H..( 1992;). Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. . Nature 357: 417–420. [CrossRef] [PubMed]
    [Google Scholar]
  9. Delmas B., Gelfi J., Kut E., Sjöström H., Noren O., Laude H..( 1994;). 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 68: 5216–5224.[PubMed]
    [Google Scholar]
  10. Hofmann M., Wyler R..( 1988;). Propagation of the virus of porcine epidemic diarrhea in cell culture. . J Clin Microbiol 26: 2235–2239.[PubMed]
    [Google Scholar]
  11. Holmes K. V, Compton S. R..( 1995;). Coronavirus receptors. . In The Coronaviridae, pp. 55–71. Edited by Siddell S. G.. New York, NY:: Plenum Press;.[CrossRef]
    [Google Scholar]
  12. Huang Y. W., Dickerman A. W., Piñeyro P., Li L., Fang L., Kiehne R., Opriessnig T., Meng X. J..( 2013;). Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States. . MBio 4:,e0073713. [CrossRef] [PubMed]
    [Google Scholar]
  13. Hussey R. E., Richardson N. E., Kowalski M., Brown N. R., Chang H. C., Siliciano R. F., Dorfman T., Walker B., Sodroski J., Reinherz E. L..( 1988;). A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. . Nature 331: 78–81. [CrossRef] [PubMed]
    [Google Scholar]
  14. Islam M. T., Kubota T., Ujike M., Yahara Y., Taguchi F..( 2016;). Phylogenetic and antigenic characterization of newly isolated porcine epidemic diarrhea viruses in Japan. . Virus Res 222: 113–119. [CrossRef] [PubMed]
    [Google Scholar]
  15. Kaplan G., Peters D., Racaniello V. R..( 1990;). Poliovirus mutants resistant to neutralization with soluble cell receptors. . Science 250: 1596–1599. [CrossRef] [PubMed]
    [Google Scholar]
  16. Kawase M., Shirato K., Matsuyama S., Taguchi F..( 2009;). Protease-mediated entry via the endosome of human coronavirus 229E. . J Virol 83: 712–721. [CrossRef] [PubMed]
    [Google Scholar]
  17. Kawase M., Shirato K., van der Hoek L., Taguchi F., Matsuyama S..( 2012;). Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. . J Virol 86: 6537–6545. [CrossRef] [PubMed]
    [Google Scholar]
  18. Kenny A. J., Maroux S..( 1982;). Topology of microvillar membrance hydrolases of kidney and intestine. . Physiol Rev 62: 91–128.[PubMed]
    [Google Scholar]
  19. Kim O., Chae C..( 2000;). In situ hybridization for the detection and localization of porcine epidemic diarrhea virus in the intestinal tissues from naturally infected piglets. . Vet Pathol 37: 62–67. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kusanagi K., Kuwahara H., Katoh T., Nunoya T., Ishikawa Y., Samejima T., Tajima M..( 1992;). Isolation and serial propagation of porcine epidemic diarrhea virus in cell cultures and partial characterization of the isolate. . J Vet Med Sci 54: 313–318. [CrossRef] [PubMed]
    [Google Scholar]
  21. Lai M. M., Cavanagh D..( 1997;). The molecular biology of coronaviruses. . Adv Virus Res 48: 1–100.[PubMed] [CrossRef]
    [Google Scholar]
  22. Li B. X., Ge J. W., Li Y. J..( 2007;). Porcine aminopeptidase N is a functional receptor for the PEDV coronavirus. . Virology 365: 166–172. [CrossRef] [PubMed]
    [Google Scholar]
  23. Li W., Moore M. J., Vasilieva N., Sui J., Wong S. K., Berne M. A., Somasundaran M., Sullivan J. L., Luzuriaga K. et al.( 2003;). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. . Nature 426: 450–454. [CrossRef] [PubMed]
    [Google Scholar]
  24. Li W., Li H., Liu Y., Pan Y., Deng F., Song Y., Tang X., He Q..( 2012;). New variants of porcine epidemic diarrhea virus, China, 2011. . Emerg Infect Dis 18: 1350–1353. [CrossRef] [PubMed]
    [Google Scholar]
  25. Liu C., Tang J., Ma Y., Liang X., Yang Y., Peng G., Qi Q., Jiang S., Li J. et al.( 2015;). Receptor usage and cell entry of porcine epidemic diarrhea coronavirus. . J Virol 89: 6121–6125. [CrossRef] [PubMed]
    [Google Scholar]
  26. Meng F., Suo S., Zarlenga D. S., Cong Y., Ma X., Zhao Q., Ren X..( 2014;). A phage-displayed peptide recognizing porcine aminopeptidase N is a potent small molecule inhibitor of PEDV entry. . Virology 456-457: 20–27. [CrossRef] [PubMed]
    [Google Scholar]
  27. Nam E., Lee C..( 2010;). Contribution of the porcine aminopeptidase N (CD13) receptor density to porcine epidemic diarrhea virus infection. . Vet Microbiol 144: 41–50. [CrossRef] [PubMed]
    [Google Scholar]
  28. Oh J. S., Song D. S., Park B. K..( 2003;). Identification of a putative cellular receptor 150 kda polypeptide for porcine epidemic diarrhea virus in porcine enterocytes. . J Vet Sci 4: 269–275.[PubMed]
    [Google Scholar]
  29. Pan Y., Tian X., Li W., Zhou Q., Wang D., Bi Y., Chen F., Song Y..( 2012;). Isolation and characterization of a variant porcine epidemic diarrhea virus in China. . Virol J 9: 195. [CrossRef] [PubMed]
    [Google Scholar]
  30. Park J. E., Park E. S., Yu J. E., Rho J., Paudel S., Hyun B. H., Yang D. K., Shin H. J..( 2015;). Development of transgenic mouse model expressing porcine aminopeptidase N and its susceptibility to porcine epidemic diarrhea virus. . Virus Res 197: 108–115. [CrossRef] [PubMed]
    [Google Scholar]
  31. Park S. J., Moon H. J., Yang J. S., Lee C. S., Song D. S., Kang B. K., Park B. K..( 2007;). Sequence analysis of the partial spike glycoprotein gene of porcine epidemic diarrhea viruses isolated in Korea. . Virus Genes 35: 321–332. [CrossRef] [PubMed]
    [Google Scholar]
  32. Pensaert M. B., de Bouck P..( 1978;). A new coronavirus-like particle associated with diarrhea in swine. . Arch Virol 58: 243–247. [CrossRef] [PubMed]
    [Google Scholar]
  33. Puranaveja S., Poolperm P., Lertwatcharasarakul P., Kesdaengsakonwut S., Boonsoongnern A., Urairong K., Kitikoon P., Choojai P., Kedkovid R. et al.( 2009;). Chinese-like strain of porcine epidemic diarrhea virus, Thailand. . Emerg Infect Dis 15: 1112–1115. [CrossRef] [PubMed]
    [Google Scholar]
  34. Raj V. S., Mou H., Smits S. L., Dekkers D. H., Müller M. A., Dijkman R., Muth D., Demmers J. A., Zaki A. et al.( 2013;). Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. . Nature 495: 251–254. [CrossRef] [PubMed]
    [Google Scholar]
  35. Saeki K., Ohtsuka N., Taguchi F..( 1997;). Identification of spike protein residues of murine coronavirus responsible for receptor-binding activity by use of soluble receptor-resistant mutants. . J Virol 71: 9024–9031.[PubMed]
    [Google Scholar]
  36. Semenza G..( 1986;). Anchoring and biosynthesis of stalked brush border membrane proteins: glycosidases and peptidases of enterocytes and renal tubuli. . Annu Rev Cell Biol 2: 255–313. [CrossRef] [PubMed]
    [Google Scholar]
  37. Shibata I., Tsuda T., Mori M., Ono M., Sueyoshi M., Uruno K..( 2000;). Isolation of porcine epidemic diarrhea virus in porcine cell cultures and experimental infection of pigs of different ages. . Vet Microbiol 72: 173–182. [CrossRef] [PubMed]
    [Google Scholar]
  38. Shirato K., Maejima M., Hirai A., Ami Y., Takeyama N., Tsuchiya K., Kusanagi K., Nunoya T., Taguchi F..( 2010;). Enhanced cell fusion activity in porcine epidemic diarrhea virus adapted to suckling mice. . Arch Virol 155: 1989–1995. [CrossRef] [PubMed]
    [Google Scholar]
  39. Shirato K., Matsuyama S., Ujike M., Taguchi F..( 2011;). Role of proteases in the release of porcine epidemic diarrhea virus from infected cells. . J Virol 85: 7872–7880. [CrossRef] [PubMed]
    [Google Scholar]
  40. Sun R. Q., Cai R. J., Chen Y. Q., Liang P. S., Chen D. K., Song C. X..( 2012;). Outbreak of porcine epidemic diarrhea in suckling piglets, China. . Emerg Infect Dis 18: 161–163. [CrossRef] [PubMed]
    [Google Scholar]
  41. Tresnan D. B., Levis R., Holmes K. V..( 1996;). Feline aminopeptidase N serves as a receptor for feline, canine, porcine, and human coronaviruses in serogroup I. . J Virol 70: 8669–8674.[PubMed]
    [Google Scholar]
  42. Turgeon D. C., Morin M., Jolette J., Higgins R., Marsolais G., DiFranco E..( 1980;). Coronavirus-like particles associated with diarrhea in baby pigs in Quebec. . Can Vet J 21: 100–xxiii.[PubMed]
    [Google Scholar]
  43. Umezawa H., Aoyagi T., Suda H., Hamada M., Takeuchi T..( 1976;). Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes. . J Antibiot (Tokyo) 29: 97–99. [CrossRef] [PubMed]
    [Google Scholar]
  44. Vui D. T., Tung N., Inui K., Slater S., Nilubol D..( 2014;). Complete genome sequence of porcine epidemic diarrhea virus in Vietnam. . Genome Announc 2:,e00753-14. [CrossRef] [PubMed]
    [Google Scholar]
  45. Wang L., Byrum B., Zhang Y..( 2014;). New variant of porcine epidemic diarrhea virus, United States, 2014. . Emerg Infect Dis 20: 917–919. [CrossRef] [PubMed]
    [Google Scholar]
  46. Watanabe R., Matsuyama S., Shirato K., Maejima M., Fukushi S., Morikawa S., Taguchi F..( 2008;). Entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved S protein as revealed by pseudotype virus bearing cleaved S protein. . J Virol 82: 11985–11991. [CrossRef] [PubMed]
    [Google Scholar]
  47. Weiss S. R., Navas-Martin S..( 2005;). Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. . Microbiol Mol Biol Rev 69: 635–664. [CrossRef] [PubMed]
    [Google Scholar]
  48. Williams R. K., Jiang G. S., Holmes K. V..( 1991;). Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. . Proc Natl Acad Sci U S A 88: 5533–5536. [CrossRef] [PubMed]
    [Google Scholar]
  49. Würdinger T., Verheije M. H., Raaben M., Bosch B. J., de Haan C. A., van Beusechem V. W., Rottier P. J., Gerritsen W. R..( 2005;). Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody. . Gene Ther 12: 1394–1404. [CrossRef] [PubMed]
    [Google Scholar]
  50. Yang C. W., Yang Y. N., Liang P. H., Chen C. M., Chen W. L., Chang H. Y., Chao Y. S., Lee S. J..( 2007;). Novel small-molecule inhibitors of transmissible gastroenteritis virus. . Antimicrob Agents Chemother 51: 3924–3931. [CrossRef] [PubMed]
    [Google Scholar]
  51. Yeager C. L., Ashmun R. A., Williams R. K., Cardellichio C. B., Shapiro L. H., Look A. T., Holmes K. V..( 1992;). Human aminopeptidase N is a receptor for human coronavirus 229E. . Nature 357: 420–422. [CrossRef] [PubMed]
    [Google Scholar]
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