Integrative Transcriptomics and Proteomics Analysis Reveals Immune Response Process in Bovine Viral Diarrhea Virus-1-Infected Peripheral Blood Mononuclear Cells

SIMPLE SUMMARY: Bovine viral diarrhea virus (BVDV) is a viral pathogen that poses a significant threat to the global cattle industry. BVDV infection interferes with the host’s innate and adaptive immunity, thereby affecting the diverse organs and systems of the body. Thus, comprehending the biological mechanisms by which viruses infect hosts is pivotal for disease control and prevention. Currently, the molecular mechanisms of the cell signaling pathways affected by BVDV infection remain unclear. Transcriptomic and proteomic methods offer promising avenues to dissect the biological processes in virus-infected host cells. In this study, transcriptomics and proteomics techniques were used to analyze differentially expressed proteins and scrutinize differentially expressed genes in immune-related biological processes after BVDV-1 infection in cow peripheral blood mononuclear cells (PBMCs). Our findings indicate that BVDV-1 predominantly suppresses the host through pathways such as the interleukin-17 signaling pathway, cytokine-cytokine receptor interaction, and complement and coagulation cascades. Conversely, PBMCs seem to counter viral invasion through mechanisms such as complement and coagulation cascades, the RIG-I-like receptor signaling pathway, and cytokine-cytokine receptor interaction. This study forms a theoretical basis for analyzing the mechanism of BVDV-1 infection and facilitates a deeper exploration of host responses to BVDV-1 infection in dairy cows. ABSTRACT: Bovine viral diarrhea virus (BVDV) causes bovine viral diarrhea-mucosal disease, inflicting substantial economic losses upon the global cattle industry. Peripheral blood mononuclear cells (PBMCs) are the central hub for immune responses during host-virus infection and have been recognized as crucial targets for BVDV infection. In order to elucidate the dynamics of host-BVDV-1 interaction, this study harnessed RNA-seq and iTRAQ methods to acquire an extensive dataset of transcriptomics and proteomics data from samples of BVDV-1-infected PBMCs at the 12-h post-infection mark. When compared to mock-infected PBMCs, we identified 344 differentially expressed genes (DEGs: a total of 234 genes with downregulated expression and 110 genes with upregulated expression) and 446 differentially expressed proteins (DEPs: a total of 224 proteins with downregulated expression and 222 proteins with upregulated expression). Selected DEGs and DEPs were validated through quantitative reverse transcriptase-polymerase chain reaction and parallel reaction monitoring. Gene ontology annotation and KEGG enrichment analysis underscored the significant enrichment of DEGs and DEPs in various immunity-related signaling pathways, including antigen processing and presentation, complement and coagulation cascades, cytokine-cytokine receptor interaction, and the NOD-like receptor signaling pathway, among others. Further analysis unveiled that those DEGs and DEPs with downregulated expression were predominantly associated with pathways such as complement and coagulation cascades, the interleukin-17 signaling pathway, cytokine-cytokine receptor interaction, the PI3K-Akt signaling pathway, the tumor necrosis factor signaling pathway, and the NOD-like receptor signaling pathway. Conversely, upregulated DEGs and DEPs were chiefly linked to metabolic pathways, oxidative phosphorylation, complement and coagulation cascades, and the RIG-I-like receptor signaling pathway. These altered genes and proteins shed light on the intense host-virus conflict within the immune realm. Our transcriptomics and proteomics data constitute a significant foundation for delving further into the interaction mechanism between BVDV and its host.