Comparative Analyses of Transcriptome Data from Beef Cattle Persistently Infected with Bovine Viral Diarrhea Virus

Persistent infection (PI) with Bovine Viral Diarrhea Virus (BVDV) is a major source of economic loss for the livestock industry. Persistent infection occurs when a dam is exposed to the virus during 42 to 125 days of gestation and the virus is passed to the fetus without an adaptive immune response. These PI calves serve as continuous sources of infection to others. The identification of differences in expression of gene networks and/or genetic markers associated with infection could assist in the development of novel strategies to prevent, control, or treat BVDV. To examine the host response to PI, RNA-Seq data were obtained from blood of cattle naturally infected and PI with BVDV strains 1a (n=10), 1b (n=8), and 2 (n=8). Additional data were collected from two comparison groups, a high exposure group with one positive test for the virus that were later confirmed negative for PI (n=9), and an unexposed group from a closed herd (n=10). Sequencing on an Illumina NextSeq resulted in 58 million stranded paired-end reads per animal which were aligned to the UMD3.1 bovine genome. With 86% of the reads aligning and the quantification of 22,915 transcripts, differential expression analyses revealed there were no significant differentially expressed transcripts between the strain subtypes and among the strains of PI cattle. There were 1,032 differentially expressed transcripts between the PIs and the high exposure group; this is the comparison that was focused on in further analyses. The differential expression data were examined for gene network relationships. The top significant canonical pathways represented by the expression data were interferon signaling and activation of interferon response factors by cytosolic pattern recognition receptors. There were significant predictions of decreased replication of viruses and decreased risk of viral infection for the BVDV-PIs. These results suggest that the BVDV-PIs may have an innate immune response to BVDV since the directionality of their gene expression supports the presence of a viral infection when compared to high exposure animals. Advisor: Jessica L. Peterse