Immunological impacts following an in-utero BVDV exposure to post-weaning calves

Maternal viral infection has profound impacts on fetal immune development and neonatal susceptibility of disease(s) in humans and livestock. Calves infected in-utero with bovine viral diarrhea virus (BVDV) during gestation are reported to have an increased susceptibility to early life infections such as bovine respiratory disease. The purpose of this study will elucidate mechanisms of the long-term immunological impact of in-utero BVDV infection. Meeting this objective, at gestation day 200 pregnant dams were exposed to BVDV or sham, resulting in the births of transiently infected (TI) and control calves. These calves were then inoculated with Mannheimia haemolytica (MH) or media via endoscopic broncho-alveolar lavage (BAL) post weaning. Calves were distributed in a two-by-two study design based on infection status. Control calves, not exposed to BVDV in-utero, inoculated with media (CRTL/CRTL, n=4), control calves inoculated with MH (CRTL/MH, n=3), TI calves, exposed to BVDV in-utero with media inoculation (TI/CRTL, n=3), and TI calves with MH inoculation (TI/MH, n=5). All groups were assigned clinical illness scores (CIS) daily with thoracic ultrasound scoring (TUS) throughout the study. BAL fluid (BALF) was collected for biomarker concentration and cytology analysis. Serum samples were collected to analyze biomarker concentrations and serology. Results found that thoracic ultrasound scores and rectal temperature correlate with MH infection status and study day supported by serology results confirming a successful experimental MH infection. However, the difference between TI calves and control calves infected with MH yielded significant correlations when comparing CIS and TUS. Significant differences were found in mean concentrations of white blood cells (WBC) and lymphocyte between study days. Treatment by study day effects from linear regression was observed in IL-1ϐ, IL-36Ra, and IP-10 from BALF samples and VEGF-A from blood serum. Linear regression between treatment groups was statistically significant in IL-1ϐ, IFNγ, IL-17A, IL-8, IL-36Ra, IP-10, and TNFα from BALF as well as IL-1α and VEGF-A in serum. Post-hoc multiple comparisons yielded statistical significance between study days in VEGF-A and MCP-1 from BALF, MCP-1 and IP-10 in blood serum and serological analysis. These findings hint at a dysfunctional immune response caused by the late gestational in-utero BVDV.