Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2023 Jan 19

PMID 36656013

Authors

Qi-Zhang Liang

Bin Wang

Chun-Miao Ji

Feifan Hu

Pan Qin

Yaoyu Feng

Yan-Dong Tang

Yao-Wei Huang

Affiliations

Soon will be listed here.

Abstract

Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, and sparrow DCoV HKU17 (Chinese strain), and PDCoV in the subgenera are grouped together at whole-genome levels; however, the spike (S) glycoprotein and its S1 subunit of HKU17 are more closely related to night heron DCoV HKU19 in . Nevertheless, the S1 protein of HKU11, HKU13, or HKU17 bound to or interacted with chicken APN (chAPN) or porcine APN (pAPN) by flow cytometry analysis of cell surface expression of APN and by coimmunoprecipitation in APN-overexpressing cells. Expression of chAPN or pAPN allowed entry of pseudotyped lentiviruses with the S proteins from HKU11, HKU13 and HKU17 into nonsusceptible cells and natural avian and porcine cells, which could be inhibited by the antibody against APN or anti-PDCoV-S1. APN knockdown by siRNA or knockout by CRISPR/Cas9 in chicken or swine cell lines significantly or almost completely blocked infection of these pseudoviruses. Hence, we demonstrate that HKU11, HKU13, and HKU17 with divergent S genes likely engage chAPN or pAPN to enter the cells, suggesting a potential interspecies transmission from wild birds to poultry and from birds to mammals by certain avian DCoVs. The receptor usage of avian deltacoronaviruses (DCoVs) has not been investigated thus far, though porcine deltacoronavirus (PDCoV) has been shown to utilize aminopeptidase N (APN) as a cell receptor. We report here that chicken or porcine APN also mediates cellular entry by three avian DCoV (HKU11, HKU13, and HKU17) spike pseudoviruses, and the S1 subunit of three avian DCoVs binds to APN and in the surface of avian and porcine cells. The results fill the gaps in knowledge about the avian DCoV receptor and elucidate important insights for the monitoring and prevention of potential interspecies transmission of certain avian DCoVs. In view of the diversity of DCoVs, whether this coronavirus genus will cause novel virus to emerge in other mammals from birds, are worthy of further surveillance and investigation.

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References

Zhang J, Chen J, Shi D, Shi H, Zhang X, Liu J . Porcine deltacoronavirus enters cells via two pathways: A protease-mediated one at the cell surface and another facilitated by cathepsins in the endosome. J Biol Chem. 2019; 294(25):9830-9843. PMC: 6597833. DOI: 10.1074/jbc.RA119.007779. View

Wang Y, Yue H, Fang W, Huang Y . Complete Genome Sequence of Porcine Deltacoronavirus Strain CH/Sichuan/S27/2012 from Mainland China. Genome Announc. 2015; 3(5). PMC: 4559728. DOI: 10.1128/genomeA.00945-15. View

Lau S, Wong E, Tsang C, Ahmed S, Au-Yeung R, Yuen K . Discovery and Sequence Analysis of Four Deltacoronaviruses from Birds in the Middle East Reveal Interspecies Jumping with Recombination as a Potential Mechanism for Avian-to-Avian and Avian-to-Mammalian Transmission. J Virol. 2018; 92(15). PMC: 6052312. DOI: 10.1128/JVI.00265-18. View

Steffen I, Simmons G . Pseudotyping Viral Vectors With Emerging Virus Envelope Proteins. Curr Gene Ther. 2016; 16(1):47-55. DOI: 10.2174/1566523216666160119093948. View

Ye X, Chen Y, Zhu X, Guo J, Xie D, Hou Z . Cross-species transmission of deltacoronavirus and the origin of porcine deltacoronavirus. Evol Appl. 2020; 13(9):2246-2253. PMC: 7273114. DOI: 10.1111/eva.12997. View

Li W, Hulswit R, Kenney S, Widjaja I, Jung K, Alhamo M . Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility. Proc Natl Acad Sci U S A. 2018; 115(22):E5135-E5143. PMC: 5984533. DOI: 10.1073/pnas.1802879115. View

Benbacer L, Kut E, Besnardeau L, Laude H, Delmas B . Interspecies aminopeptidase-N chimeras reveal species-specific receptor recognition by canine coronavirus, feline infectious peritonitis virus, and transmissible gastroenteritis virus. J Virol. 1997; 71(1):734-7. PMC: 191108. DOI: 10.1128/JVI.71.1.734-737.1997. View

Cong L, Zhang F . Genome engineering using CRISPR-Cas9 system. Methods Mol Biol. 2014; 1239:197-217. DOI: 10.1007/978-1-4939-1862-1_10. View

Wang L, Byrum B, Zhang Y . Detection and genetic characterization of deltacoronavirus in pigs, Ohio, USA, 2014. Emerg Infect Dis. 2014; 20(7):1227-30. PMC: 4073853. DOI: 10.3201/eid2007.140296. View

10.

Lu G, Wang Q, Gao G . Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV, MERS-CoV, and beyond. Trends Microbiol. 2015; 23(8):468-78. PMC: 7125587. DOI: 10.1016/j.tim.2015.06.003. View

11.

Woo P, Lau S, Huang Y, Yuen K . Coronavirus diversity, phylogeny and interspecies jumping. Exp Biol Med (Maywood). 2009; 234(10):1117-27. DOI: 10.3181/0903-MR-94. View

12.

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

13.

Marthaler D, Raymond L, Jiang Y, Collins J, Rossow K, Rovira A . Rapid detection, complete genome sequencing, and phylogenetic analysis of porcine deltacoronavirus. Emerg Infect Dis. 2014; 20(8):1347-50. PMC: 4111195. DOI: 10.3201/eid2008.140526. View

14.

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

15.

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

16.

Niu X, Hou Y, Jung K, Kong F, Saif L, Wang Q . Chimeric Porcine Deltacoronaviruses with Sparrow Coronavirus Spike Protein or the Receptor-Binding Domain Infect Pigs but Lose Virulence and Intestinal Tropism. Viruses. 2021; 13(1). PMC: 7829776. DOI: 10.3390/v13010122. View

17.

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

18.

Lau S, Zhang L, Luk H, Xiong L, Peng X, Li K . Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. J Infect Dis. 2018; 218(2):197-207. PMC: 7107427. DOI: 10.1093/infdis/jiy018. View

19.

Ji C, Wang B, Zhou J, Huang Y . Aminopeptidase-N-independent entry of porcine epidemic diarrhea virus into Vero or porcine small intestine epithelial cells. Virology. 2018; 517:16-23. PMC: 7127557. DOI: 10.1016/j.virol.2018.02.019. View

20.

Chen Q, Wang L, Yang C, Zheng Y, Gauger P, Anderson T . The emergence of novel sparrow deltacoronaviruses in the United States more closely related to porcine deltacoronaviruses than sparrow deltacoronavirus HKU17. Emerg Microbes Infect. 2018; 7(1):105. PMC: 5988828. DOI: 10.1038/s41426-018-0108-z. View