Integrated analysis of transcriptome and proteome reveal that PDCoV infection induces autophagy-dependent ferroptosis to facilitate viral replication.

Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus that causes severe diarrhea in swine industries worldwide. However, the interactions between PDCoV and host cells remain poorly understood. In this study, we employed transcriptomic and proteomic analyses to investigate host responses to PDCoV infection. Our results identified 1448 differentially expressed genes (DEGs) at 1.5 h post-PDCoV infection and 11,753 DEGs, along with 898 differentially expressed proteins (DEPs) at 18 h post-PDCoV infection. Furthermore, several signaling pathways, including innate immunity, autophagy, and ferroptosis, were primarily enriched following an integrated analysis of the transcriptome and proteome. Protein-protein interaction (PPI) analysis indicated that proteins closely associated with these pathways, such as interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), myxovirus resistance 2 (MX2), interferon-stimulated gene 15 (ISG15), radical S-adenosyl methionine domain containing 2 (RSAD2), 2'-5'-oligoadenylate synthetase like (OASL), autophagy related 14 (ATG14), and glutathione peroxidase 4 (GPX4), were central to the interaction network. Importantly, we demonstrated that autophagy and ferroptosis were induced upon PDCoV infection, and that inhibition of autophagy significantly suppressed the induction of PDCoV-induced ferroptosis, which decreases the viral proliferation. Overall, our findings provide a comprehensive overview of transcriptomic and proteomic changes following PDCoV infection and enhance the understanding of PDCoV pathogenesis, which will be beneficial for improving strategies for the prevention and control of PDCoV infection.