Exploration of Viral Pathogenesis and Immune Function Following Fetal Infection with Bovine Viral Diarrhea Virus

Author

Morgan L. Adkins, University of Tennessee, KnoxvilleFollow

Date of Award

5-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major Professor

Andrea S. Lear

Committee Members

Jon Beever, James Marc Caldwell, David Hurley

Abstract

Bovine viral diarrhea virus (BVDV) is an endemic pathogen of cattle with vast genetic heterogenicity and a myriad of clinical outcomes. Of interest is BVDV's role in Bovine Respiratory Disease Complex (BRDC) and consequences of fetal infection resulting in a persistently infected (PI) animal or transiently infected (TI) animal. While PIs are born with a chronic viremia, TIs resolve their infection status in-utero. Despite the differences in infection outcome, fetal exposure seems to alter immune function and performance. This work aims to evaluate 1) immune-related gene expression in adult PIs, 2) differences in the innate and adaptive immune systems of PI and TI calves, and 3) exosome-mediated transmission of BVDV. Targeted RNAseq analysis was performed with peripheral blood mononuclear cells (PBMCs) in 6 adult PIs. Of the 54 selected immune related genes, analysis revealed 29 differentially expressed genes and 14 significantly represented pathways (PStaphylococcus aureus bioparticles and magnetic bead cytokine multiplex of media. There was no significant difference in phagocytic ability of PI (N=4) and TI (N=5) monocytes compared to controls (N=5) but an increase in IL-36RA production from PI monocytes. At 4 months, calves received a combination vaccine and booster for BRDC pathogens. Blood was collected to measure antibody titers and PMBCs were isolated for global RNAseq analysis. Titer response did not differ by group (PI=3, TI=4, C=5), but there was a significant effect of titers over time (P<0.05).Analysis revealed 10 DEGs in TIvC, 309 DEGs in PIvC, 385 DEGs in PIvTI, with associated overrepresented pathways. The final experiment isolated exosomes in cell culture conditions using magnetic bead selection to evaluate for viral content and transmission. Results demonstrated viral content through immunoperoxidase assay and real-time quantitative PCR although not with immunofluorescence. In conclusion, fetal BVDV infection indicates alteration to immune function and exosomes to not appear to be a primary mechanism of BVDV transmission.

Recommended Citation

Adkins, Morgan L., "Exploration of Viral Pathogenesis and Immune Function Following Fetal Infection with Bovine Viral Diarrhea Virus. " PhD diss., University of Tennessee, 2025.
https://trace.tennessee.edu/utk_graddiss/12331