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Literature detail

Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility.

Wentao Li1 Ruben J G Hulswit1 Scott P Kenney2 Ivy Widjaja1 Kwonil Jung2 Moyasar A Alhamo2 Brenda van Dieren1 Frank J M van Kuppeveld1 Linda J Saif3 Berend-Jan Bosch4,5
Affiliations 5 institutions
  1. Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
  2. Department of Veterinary Preventive Medicine, Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691.
  3. Department of Veterinary Preventive Medicine, Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691 [email protected] [email protected].
  4. Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands
  5. [email protected] [email protected].
PMID 29760102 2018 Proc Natl Acad Sci U S A eng ppublish
PubMed DOI Browse context

Article

Publication summary

Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the <i>Deltacoronavirus</i> genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the <i>Alphacoronavirus</i> genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.

APN cross-species transmission PDCoV receptor spike Communicable Diseases, Emerging Coronavirus Infections Animals Antibodies, Viral Cats CD13 Antigens Cell Line Chickens Chlorocebus aethiops Coronavirus Dogs Host Specificity Host-Pathogen Interactions

Structured evidence records

Evidence records

8 total
Host Range Experiment 4 records
Host Range Experiment Extraction confidence 0.95
Key finding

Porcine deltacoronavirus was shown to infect cells from pigs, humans, and chickens, with APN receptor expression determining susceptibility.

Virus
PDCoV
Location
Not specified
Supporting text

Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection.

Method
infection assay; receptor expression assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.95
Key finding

Porcine deltacoronavirus was shown to infect chicken cells, with APN receptor expression enabling susceptibility.

Virus
PDCoV
Location
Not specified
Supporting text

Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection.

Method
infection assay; receptor expression assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.95
Key finding

Porcine deltacoronavirus replicates in porcine cells through APN-mediated entry, shown by loss of infection after APN knockout and restoration after APN reconstitution.

Virus
PDCoV
Location
Not specified
Supporting text

Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection.

Method
infection assay; gene knockout; receptor reconstitution assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.90
Key finding

Transient expression of feline APN confers susceptibility to PDCoV infection in vitro, demonstrating receptor-mediated host range expansion.

Virus
PDCoV
Location
Not specified
Supporting text

Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection.

Method
transient expression; infection assay
Experimental system
in vitro cell culture
Receptor Usage 2 records
Receptor Usage Extraction confidence 1.00
Key finding

Porcine deltacoronavirus uses aminopeptidase N as an entry receptor, with spike domain B mediating interaction.

Virus
PDCoV
Location
Not specified
Supporting text

Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression.

Method
APN knockout; reconstitution of APN expression
Receptors
aminopeptidase N (APN)
Receptor Usage Extraction confidence 1.00
Key finding

Expression of APN from multiple species enables PDCoV infection, indicating conserved receptor compatibility across hosts.

Virus
PDCoV
Location
Not specified
Supporting text

Transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. PDCoV S was found to target the phylogenetically conserved catalytic domain of APN.

Method
transient expression assay
Receptors
aminopeptidase N (APN)
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.90
Key finding

Porcine deltacoronavirus evolved through a host-switching event between avian and mammalian species.

Virus
PDCoV
Host
Mammalia Aves
Location
Not specified
Supporting text

Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals.

Method
phylogenetic analysis
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.80
Key finding

Porcine deltacoronavirus phylogenetically clusters in a way indicating a recent host switch between birds and mammals.

Virus
PDCoV
Host
Aves
Location
Not specified
Supporting text

Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals.

Analysis methods
phylogenetic analysis