Porcine Epidemic Diarrhea Virus Replication in Human Intestinal Cells Reveals Potential Susceptibility to Cross-Species Infection

Various coronaviruses have emerged as a result of cross-species transmission among humans and domestic animals. Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea, vomiting, dehydration, and high mortality in neonatal piglets. Porcine small intestinal epithelial cells (IPEC-J2 cells) can be used as target cells for PEDV infection. However, the origin of PEDV in pigs, the host range, and cross-species infection of PEDV remain unclear. To determine whether PEDV has the ability to infect human cells in vitro, human small intestinal epithelial cells (FHs 74 Int cells) were inoculated with PEDV LJX and PEDV CV777 strains. The results indicated that PEDV LJX, but not PEDV CV777, could infect FHs 74 Int cells. Furthermore, we observed M gene mRNA transcripts and N protein expression in infected FHs 74 Int cells. A one-step growth curve showed that the highest viral titer of PEDV occurred at 12 h post infection. Viral particles in vacuoles were observed in FHs 74 Int cells at 24 h post infection. The results proved that human small intestinal epithelial cells are susceptible to PEDV infection, suggesting the possibility of cross-species transmission of PEDV.

[1]  R. Baric,et al.  Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection , 2022, Proceedings of the National Academy of Sciences of the United States of America.

[2]  E. Holmes,et al.  The origins of SARS-CoV-2: A critical review , 2021, Cell.

[3]  Shou-Jiang Gao,et al.  SARS‐CoV‐2 pseudovirus infectivity and expression of viral entry‐related factors ACE2, TMPRSS2, Kim‐1, and NRP‐1 in human cells from the respiratory, urinary, digestive, reproductive, and immune systems , 2021, Journal of medical virology.

[4]  Sudhir Kumar,et al.  MEGA11: Molecular Evolutionary Genetics Analysis Version 11 , 2021, Molecular biology and evolution.

[5]  M. Pomorska-Mól,et al.  Porcine Coronaviruses: Overview of the State of the Art , 2021, Virologica Sinica.

[6]  A. Miyazaki,et al.  Systemic and intestinal porcine epidemic diarrhea virus-specific antibody response and distribution of antibody-secreting cells in experimentally infected conventional pigs , 2021, Veterinary Research.

[7]  G. Gao,et al.  Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2 , 2020, Cell discovery.

[8]  Siru Liu,et al.  The management of coronavirus disease 2019 (COVID‐19) , 2020, Journal of medical virology.

[9]  Hans Clevers,et al.  SARS-CoV-2 productively infects human gut enterocytes , 2020, Science.

[10]  Kai Zhao,et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin , 2020, Nature.

[11]  Jiyong Zhou,et al.  Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission , 2019, Journal of Virology.

[12]  Qian Yang,et al.  An alternative pathway of enteric PEDV dissemination from nasal cavity to intestinal mucosa in swine , 2018, Nature Communications.

[13]  M. Lutman,et al.  Spillover of Swine Coronaviruses, United States , 2018, Emerging infectious diseases.

[14]  L. Saif,et al.  Immunohistochemical detection of the vomiting-inducing monoamine neurotransmitter serotonin and enterochromaffin cells in the intestines of conventional or gnotobiotic (Gn) pigs infected with porcine epidemic diarrhea virus (PEDV) and serum cytokine responses of Gn pigs to acute PEDV infection , 2018, Research in Veterinary Science.

[15]  B. Bosch,et al.  Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility , 2018, Proceedings of the National Academy of Sciences.

[16]  Li Feng,et al.  Porcine Epidemic Diarrhea Virus-Induced Epidermal Growth Factor Receptor Activation Impairs the Antiviral Activity of Type I Interferon , 2018, Journal of Virology.

[17]  P. Gauger,et al.  Evidence of porcine epidemic diarrhea virus (PEDV) shedding in semen from infected specific pathogen-free boars , 2018, Veterinary Research.

[18]  D. Hui,et al.  Middle East Respiratory Syndrome , 2017 .

[19]  S. Xiao,et al.  Porcine epidemic diarrhea in China , 2016, Virus Research.

[20]  Lisa E. Gralinski,et al.  A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence , 2015, Nature Medicine.

[21]  G. Gao,et al.  Bat-to-human: spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond , 2015, Trends in Microbiology.

[22]  Shibo Jiang,et al.  Receptor Usage and Cell Entry of Porcine Epidemic Diarrhea Coronavirus , 2015, Journal of Virology.

[23]  Herman Tse,et al.  Cross-reactive antibodies in convalescent SARS patients' sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests , 2013, Journal of Infection.

[24]  Songnian Hu,et al.  EvolView, an online tool for visualizing, annotating and managing phylogenetic trees , 2012, Nucleic Acids Res..

[25]  Xiaojie Guo,et al.  Seroepidemiology of group I human coronaviruses in children , 2007, Journal of Clinical Virology.

[26]  X. Meng,et al.  Antigenic Cross-Reactivity between the Nucleocapsid Protein of Severe Acute Respiratory Syndrome (SARS) Coronavirus and Polyclonal Antisera of Antigenic Group I Animal Coronaviruses: Implication for SARS Diagnosis , 2004, Journal of Clinical Microbiology.

[27]  Theo M Bestebroer,et al.  A previously undescribed coronavirus associated with respiratory disease in humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Hui,et al.  Severe acute respiratory syndrome and Toronto , 2003, Journal of epidemiology and community health.

[29]  K. Sato,et al.  An immunohistochemical investigation of porcine epidemic diarrhoea , 1995, Journal of Comparative Pathology.

[30]  D. Chasey,et al.  Virus-like particles associated with porcine epidemic diarrhoea , 1978, Research in Veterinary Science.

[31]  M. Ackermann,et al.  Studies on the in vitro and in vivo host range of porcine epidemic diarrhoea virus. , 1995, Advances in experimental medicine and biology.