Porcine Aminopeptidase N is a Functional Receptor for the PEDV Coronavirus

Overview

Journal Virology

Specialty Microbiology

Date 2007 May 1

PMID 17467767

Citations 128

Authors

B X Li

J W Ge

Y J Li

Affiliations

Soon will be listed here.

Abstract

Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in piglets that leads to great economic losses in East Asia. It was reported that aminopeptidase N (APN) is the receptor for transmissible gastroenteritis virus (TGEV), human coronavirus 229E (HCoV-229E) and feline coronavirus (FeCoV) which all belong to group I coronavirus including as well as PEDV. It was also confirmed previously that porcine aminopeptidase N (pAPN) can bind to PEDV, and anti-pAPN antibodies may inhibit the combination. To investigate whether pAPN is a receptor for PEDV, we transfected MDCK cells with porcine aminopeptidase (pAPN) cDNA and this enabled non-susceptible cells to support PEDV replication and serial viral propagation. Moreover, the infection was blocked by antibodies against pAPN, implies the critical role of pAPN during virus entry. In addition, immunofluorescence assays for detection of pAPN and PEDV antigens, together with neutralization assays using antibodies against pAPN, further confirmed the correlation between pAPN expression and viral replication in pAPN-transfected MDCK cells. These results indicate that pAPN is a functional receptor for PEDV.

Citing Articles

Lactoferrin exhibits PEDV antiviral activity by interfering with spike-heparan sulfate proteoglycans binding and activating mucosal immune response.

Liu P, Zuo J, Lu H, Zhang B, Wu C Vet Res. 2025; 56(1):25.

PMID: 39891300 PMC: 11786531. DOI: 10.1186/s13567-025-01456-5.

FSTL1 and TLR4 interact with PEDV structural proteins to promote virus adsorption to host cells.

Liu C, Kong N, Liu H, Zhang Y, Qin W, Zhao W J Virol. 2024; 99(1):e0183724.

PMID: 39670742 PMC: 11784190. DOI: 10.1128/jvi.01837-24.

Research progress of porcine epidemic diarrhea virus S protein.

Luo H, Liang Z, Lin J, Wang Y, Liu Y, Mei K Front Microbiol. 2024; 15:1396894.

PMID: 38873162 PMC: 11169810. DOI: 10.3389/fmicb.2024.1396894.

Evolution and virulence of porcine epidemic diarrhea virus following in vitro and in vivo propagation.

Jermsutjarit P, Mebumroong S, Watcharavongtip P, Lin H, Tantituvanont A, Kaeoket K Sci Rep. 2024; 14(1):12279.

PMID: 38811677 PMC: 11137156. DOI: 10.1038/s41598-024-62875-6.

Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses.

Rosas-Murrieta N, Rodriguez-Enriquez A, Herrera-Camacho I, Millan-Perez-Pena L, Santos-Lopez G, Rivera-Benitez J Viruses. 2024; 16(2).

PMID: 38400014 PMC: 10892376. DOI: 10.3390/v16020238.

References

Werner A, Winskowsky G, Kurth R . Soluble CD4 enhances simian immunodeficiency virus SIVagm infection. J Virol. 1990; 64(12):6252-6. PMC: 248800. DOI: 10.1128/JVI.64.12.6252-6256.1990. View

Anderson B, Nakamura T, Russell S, Peng K . High CD46 receptor density determines preferential killing of tumor cells by oncolytic measles virus. Cancer Res. 2004; 64(14):4919-26. DOI: 10.1158/0008-5472.CAN-04-0884. View

Sanchez C, Gebauer F, Sune C, Mendez A, Dopazo J, Enjuanes L . Genetic evolution and tropism of transmissible gastroenteritis coronaviruses. Virology. 1992; 190(1):92-105. PMC: 7131265. DOI: 10.1016/0042-6822(92)91195-z. View

Delmas B, Gelfi J, Kut E, Sjostrom 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; 68(8):5216-24. PMC: 236465. DOI: 10.1128/JVI.68.8.5216-5224.1994. View

Song D, Yang J, Oh J, Han J, Park B . Differentiation of a Vero cell adapted porcine epidemic diarrhea virus from Korean field strains by restriction fragment length polymorphism analysis of ORF 3. Vaccine. 2003; 21(17-18):1833-42. PMC: 7173220. DOI: 10.1016/s0264-410x(03)00027-6. View

Hofmann M, Wyler R . Propagation of the virus of porcine epidemic diarrhea in cell culture. J Clin Microbiol. 1988; 26(11):2235-9. PMC: 266866. DOI: 10.1128/jcm.26.11.2235-2239.1988. View

Reynes J, Portales P, Segondy M, Baillat V, Andre P, Reant B . CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. J Infect Dis. 2000; 181(3):927-32. DOI: 10.1086/315315. View

Schultze B, Enjuanes L, Herrler G . Analysis of the sialic acid-binding activity of the transmissible gastroenteritis virus. Adv Exp Med Biol. 1995; 380:367-70. DOI: 10.1007/978-1-4615-1899-0_59. View

Bosch B, van der Zee R, de Haan C, Rottier P . The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J Virol. 2003; 77(16):8801-11. PMC: 167208. DOI: 10.1128/jvi.77.16.8801-8811.2003. View

10.

Oh J, Song D, Park B . Identification of a putative cellular receptor 150 kDa polypeptide for porcine epidemic diarrhea virus in porcine enterocytes. J Vet Sci. 2003; 4(3):269-75. View

11.

YEAGER C, Ashmun R, Williams R, Cardellichio C, Shapiro L, Look A . Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992; 357(6377):420-2. PMC: 7095410. DOI: 10.1038/357420a0. View

12.

Delmas B, Gelfi J, LHaridon R, Vogel L, Sjostrom H, Noren O . Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature. 1992; 357(6377):417-20. PMC: 7095137. DOI: 10.1038/357417a0. View

13.

Olsen J, Sjostrom H, Noren 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; 251(1-2):275-81. DOI: 10.1016/0014-5793(89)81470-x. View

14.

Junwei G, Baoxian L, Lijie T, Yijing L . Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03. Virus Genes. 2006; 33(2):215-9. PMC: 7089218. DOI: 10.1007/s11262-005-0059-z. View

15.

Tresnan D, Levis R, Holmes K . Feline aminopeptidase N serves as a receptor for feline, canine, porcine, and human coronaviruses in serogroup I. J Virol. 1996; 70(12):8669-74. PMC: 190961. DOI: 10.1128/JVI.70.12.8669-8674.1996. View

16.

Tresnan D, Holmes K . Feline aminopeptidase N is a receptor for all group I coronaviruses. Adv Exp Med Biol. 1998; 440:69-75. DOI: 10.1007/978-1-4615-5331-1_9. View

17.

Schenten D, Marcon L, Karlsson G, Parolin C, Kodama T, Gerard N . Effects of soluble CD4 on simian immunodeficiency virus infection of CD4-positive and CD4-negative cells. J Virol. 1999; 73(7):5373-80. PMC: 112593. DOI: 10.1128/JVI.73.7.5373-5380.1999. View

18.

Kolb A, Hegyi A, Maile J, Heister A, Hagemann M, Siddell S . Molecular analysis of the coronavirus-receptor function of aminopeptidase N. Adv Exp Med Biol. 1998; 440:61-7. DOI: 10.1007/978-1-4615-5331-1_8. View

19.

Hansen G, Delmas B, Besnardeau L, Vogel L, Laude H, Sjostrom H . The coronavirus transmissible gastroenteritis virus causes infection after receptor-mediated endocytosis and acid-dependent fusion with an intracellular compartment. J Virol. 1998; 72(1):527-34. PMC: 109404. DOI: 10.1128/JVI.72.1.527-534.1998. View

20.

Delmas B, Gelfi J, Sjostrom H, Noren O, Laude H . Further characterization of aminopeptidase-N as a receptor for coronaviruses. Adv Exp Med Biol. 1993; 342:293-8. DOI: 10.1007/978-1-4615-2996-5_45. View