Integrative transcriptomic and proteomic analyses reveal that carbon metabolism and complement system of Madin Darby Bovine Kidney cells are affected by bovine coronavirus infection.

Abstract

Background: Bovine coronavirus (BCoV) is a major pathogen of bovine respiratory disease, causing respiratory and enteric infections in cattle and wild ruminants. It is responsible for economic losses and threatens the health and welfare of cattle industry.

Results: In this study, a BCoV isolate, BCoV/SUWN/XHD-5, had cytopathogenic effects in Madin Darby bovine kidney (MDBK) cells and showed a high viral titer at 24 and 48 h post infection (hpi). Gene expression profiling using RNA sequencing and protein network mapping using the Tandem Mass Tag-based quantitative proteomics approach were performed in MDBK cells with BCoV infection at 24 and 48 hpi, respectively. Compared with mock-infected MDBK cells, 8,720 differentially expressed genes (DEGs) and 296 differentially expressed proteins (DEPs) were identified in BCoV infection at 24 hpi, whereas 5,838 DEGs and 747 DEPs were identified in BCoV infection at 48 hpi. Following GO annotation and KEGG enrichment analysis, most DEGs and DEPs were significantly enriched in metabolic pathways, endocytosis, ribosome and protein processing in endoplasmic reticulum, apoptosis and immune response. A correlation analysis of the proteome and transcriptome revealed that the up-regulated DEGs and DEPs were predominantly associated with metabolic pathways, apoptosis and the MAPK/TNF/Ras signaling pathway, whereas the down-regulated DEGs and DEPs were involved in complement and coagulation cascades and the Wnt signaling pathway. Importantly, BCoV decreases the mRNA and protein levels of complement component C3 in MDBK cells.

Conclusions: The findings of this study provide the first report of the integrative transcriptomic and proteomic analyses of BCoV infection in MDBK cells. It revealed a regulatory network for analyzing the mechanisms of BCoV-host interactions and provides valuable insights into the pathogenesis of BCoV.