Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection

Porcine deltacoronavirus (PDCoV) is an emerging infectious disease of swine with zoonotic potential. Phylogenetic analysis suggests that PDCoV originated recently from a host-switching event between birds and mammals. Little is known about how PDCoV interacts with its differing hosts. Human-derived...

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Main Authors: Diana Cruz-Pulido, Patricia A. Boley, Wilberforce Zachary Ouma, Moyasar A. Alhamo, Linda J. Saif, Scott P. Kenney
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/2/292
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author Diana Cruz-Pulido
Patricia A. Boley
Wilberforce Zachary Ouma
Moyasar A. Alhamo
Linda J. Saif
Scott P. Kenney
author_facet Diana Cruz-Pulido
Patricia A. Boley
Wilberforce Zachary Ouma
Moyasar A. Alhamo
Linda J. Saif
Scott P. Kenney
author_sort Diana Cruz-Pulido
collection DOAJ
description Porcine deltacoronavirus (PDCoV) is an emerging infectious disease of swine with zoonotic potential. Phylogenetic analysis suggests that PDCoV originated recently from a host-switching event between birds and mammals. Little is known about how PDCoV interacts with its differing hosts. Human-derived cell lines are susceptible to PDCoV infection. Herein, we compare the gene expression profiles of an established host swine cells to potential emerging host human cells after infection with PDCoV. Cell lines derived from intestinal lineages were used to reproduce the primary sites of viral infection in the host. Porcine intestinal epithelial cells (IPEC-J2) and human intestinal epithelial cells (HIEC) were infected with PDCoV. RNA-sequencing was performed on total RNA extracted from infected cells. Human cells exhibited a more pronounced response to PDCoV infection in comparison to porcine cells with more differentially expressed genes (DEGs) in human, 7486, in comparison to pig cells, 1134. On the transcriptional level, the adoptive host human cells exhibited more DEGs in response to PDCoV infection in comparison to the primary pig host cells, where different types of cytokines can control PDCoV replication and virus production. Key immune-associated DEGs and signaling pathways are shared between human and pig cells during PDCoV infection. These included genes related to the NF-kappa-B transcription factor family, the interferon (IFN) family, the protein-kinase family, and signaling pathways such as the apoptosis signaling pathway, JAK-STAT signaling pathway, inflammation/cytokine–cytokine receptor signaling pathway. MAP4K4 was unique in up-regulated DEGs in humans in the apoptosis signaling pathway. While similarities exist between human and pig cells in many pathways, our research suggests that the adaptation of PDCoV to the porcine host required the ability to down-regulate many response pathways including the interferon pathway. Our findings provide an important foundation that contributes to an understanding of the mechanisms of PDCoV infection across different hosts. To our knowledge, this is the first report of transcriptome analysis of human cells infected by PDCoV.
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spelling doaj.art-876b310590384245b4206b4aa93d0f862023-12-11T16:56:17ZengMDPI AGViruses1999-49152021-02-0113229210.3390/v13020292Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus InfectionDiana Cruz-Pulido0Patricia A. Boley1Wilberforce Zachary Ouma2Moyasar A. Alhamo3Linda J. Saif4Scott P. Kenney5Department of Veterinary Preventive Medicine, Food Animal Health Research Program (FAHRP), Wooster, OH 44691, USADepartment of Veterinary Preventive Medicine, Food Animal Health Research Program (FAHRP), Wooster, OH 44691, USAThe Ohio Supercomputer Center (OSC), Columbus, OH 43212, USADepartment of Veterinary Preventive Medicine, Food Animal Health Research Program (FAHRP), Wooster, OH 44691, USADepartment of Veterinary Preventive Medicine, Food Animal Health Research Program (FAHRP), Wooster, OH 44691, USADepartment of Veterinary Preventive Medicine, Food Animal Health Research Program (FAHRP), Wooster, OH 44691, USAPorcine deltacoronavirus (PDCoV) is an emerging infectious disease of swine with zoonotic potential. Phylogenetic analysis suggests that PDCoV originated recently from a host-switching event between birds and mammals. Little is known about how PDCoV interacts with its differing hosts. Human-derived cell lines are susceptible to PDCoV infection. Herein, we compare the gene expression profiles of an established host swine cells to potential emerging host human cells after infection with PDCoV. Cell lines derived from intestinal lineages were used to reproduce the primary sites of viral infection in the host. Porcine intestinal epithelial cells (IPEC-J2) and human intestinal epithelial cells (HIEC) were infected with PDCoV. RNA-sequencing was performed on total RNA extracted from infected cells. Human cells exhibited a more pronounced response to PDCoV infection in comparison to porcine cells with more differentially expressed genes (DEGs) in human, 7486, in comparison to pig cells, 1134. On the transcriptional level, the adoptive host human cells exhibited more DEGs in response to PDCoV infection in comparison to the primary pig host cells, where different types of cytokines can control PDCoV replication and virus production. Key immune-associated DEGs and signaling pathways are shared between human and pig cells during PDCoV infection. These included genes related to the NF-kappa-B transcription factor family, the interferon (IFN) family, the protein-kinase family, and signaling pathways such as the apoptosis signaling pathway, JAK-STAT signaling pathway, inflammation/cytokine–cytokine receptor signaling pathway. MAP4K4 was unique in up-regulated DEGs in humans in the apoptosis signaling pathway. While similarities exist between human and pig cells in many pathways, our research suggests that the adaptation of PDCoV to the porcine host required the ability to down-regulate many response pathways including the interferon pathway. Our findings provide an important foundation that contributes to an understanding of the mechanisms of PDCoV infection across different hosts. To our knowledge, this is the first report of transcriptome analysis of human cells infected by PDCoV.https://www.mdpi.com/1999-4915/13/2/292porcine deltacoronavirusPDCoVRNAseqzoonosiscoronaviruscross-species transmission
spellingShingle Diana Cruz-Pulido
Patricia A. Boley
Wilberforce Zachary Ouma
Moyasar A. Alhamo
Linda J. Saif
Scott P. Kenney
Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection
Viruses
porcine deltacoronavirus
PDCoV
RNAseq
zoonosis
coronavirus
cross-species transmission
title Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection
title_full Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection
title_fullStr Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection
title_full_unstemmed Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection
title_short Comparative Transcriptome Profiling of Human and Pig Intestinal Epithelial Cells after Porcine Deltacoronavirus Infection
title_sort comparative transcriptome profiling of human and pig intestinal epithelial cells after porcine deltacoronavirus infection
topic porcine deltacoronavirus
PDCoV
RNAseq
zoonosis
coronavirus
cross-species transmission
url https://www.mdpi.com/1999-4915/13/2/292
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