Comprehensive transcriptomic and metabolomic analysis of porcine intestinal epithelial cells after PDCoV infection.

Introduction: Porcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. However, the underlying pathogenic mechanisms of PDCoV infection and the effects of PDCoV infection on host transcripts and metabolites remain incompletely understood. Methods: This study investigated a combined transcriptomic and metabolomic analysis of porcine intestinal epithelial cells (IPEC-J2) following PDCoV infection by LC/MS and RNA-seq techniques. A total of 1,401 differentially expressed genes and 254 differentially accumulated metabolites were detected in the comparison group of PDCoV-infected vs. mock-infected. Results and discussion: We found that PDCoV infection regulates gene sets associated with multiple signaling pathways, including the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, MAPK signaling pathway, chemokine signaling pathway, ras signaling pathway and so on. Besides, the metabolomic results showed that biosynthesis of cofactors, nucleotide metabolism, protein digestion and absorption, and biosynthesis of amino acid were involved in PDCoV infection. Moreover, integrated transcriptomics and metabolomics analyses revealed the involvement of ferroptosis in PDCoV infection, and exogenous addition of the ferroptosis activator erastin significantly inhibited PDCoV replication. Overall, these unique transcriptional and metabolic reprogramming features may provide a better understanding of PDCoV-infected IPEC-J2 cells and potential targets for antiviral treatment.