RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

Simple Summary Due to the undeniable detrimental impact of bovine viral diarrhea virus (BVDV) on cattle worldwide, various preventive approaches are carried out to control the spread of this disease. Among the established preventive approaches, vaccination remains the most widely used cost-effective method of control. Hence, a deeper study into the host immune response to vaccines will further refine the efficacy of these vaccines; the identification of differentially expressed genes (DEGs) related to immune response might bring a long-lasting solution. Thus far, studies showing the genes related to the immune response of cattle to vaccines are still limited. Therefore, this study identified DEGs in animals with high and low sample to positive (S/P) ratio based on the BVDV antibody level, using RNA sequencing (RNA-seq) transcriptome analysis, and functional enrichment analysis in gene ontology (GO) annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results revealed that several upregulated and downregulated genes were significantly annotated to antigen processing and presentation (MHC class I), immune response, and interferon-gamma production, indicating the immune response of the animals related to possible shaping of their adaptive immunity against the BVDV type I. Moreover, significant enrichment to various KEGG pathways related to the development of adaptive immunity was observed. Immune response of 107 vaccinated Holstein cattle was initially obtained prior to the ELISA test. Five cattle with high and low bovine viral diarrhea virus (BVDV) type I antibody were identified as the final experimental animals. Blood samples from these animals were then utilized to determine significant differentially expressed genes (DEGs) using the RNA-seq transcriptome analysis and enrichment analysis. Our analysis identified 261 DEGs in cattle identified as experimental animals. Functional enrichment analysis in gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the DEGs potentially induced by the inactivated BVDV type I vaccine, and might be responsible for the host immune responses. Our findings suggested that inactivated vaccine induced upregulation of genes involved in different GO annotations, including antigen processing and presentation of peptide antigen (via MHC class I), immune response, and positive regulation of interferon-gamma production. The observed downregulation of other genes involved in immune response might be due to inhibition of toll-like receptors (TLRs) by the upregulation of the Bcl-3 gene. Meanwhile, the result of KEGG pathways revealed that the majority of DEGs were upregulated and enriched to different pathways, including cytokine-cytokine receptor interaction, platelet activation, extracellular matrix (ECM) receptor interaction, hematopoietic cell lineage, and ATP-binding cassette (ABC) transporters. These significant pathways supported our initial findings and are known to play a vital role in shaping adaptive immunity against BVDV type 1. In addition, type 1 diabetes mellitus pathways tended to be significantly enriched. Thus, further studies are needed to investigate the prevalence of type 1 diabetes mellitus in cattle vaccinated with inactivated and live BVDV vaccine.