Attenuated lymphocyte activation leads to the development of immunotolerance in bovine fetuses persistently infected with BVDV

Bovine viral diarrhea virus (BVDV) continues to cost the cattle industry millions of dollars each year despite control measures. The primary reservoirs for BVDV are persistently infected (PI) animals, which are infected in utero and shed the virus throughout their lifetime. The difficulty in controlling the virus stems from a limited understanding of transplacental transmission and fetal development of immunotolerance. In this study, pregnant BVDV naive heifers were inoculated with BVDV on day 75 of gestation and fetal spleens were collected on gestational days 82, 97, 190, and 245. Microarray analysis on splenic RNA from days 82 and 97 revealed an increase in signaling for the innate immune system and antigen presentation to T cells in day 97 PI fetuses compared to controls. RT-qPCR on select targets validated the microarray revealing a downregulation of type I interferons and lymphocyte markers in day 190 PI fetuses compared to controls. Protein was visualized using western blot and tissue sections were analyzed with HE however, the mechanisms responsible for the immunotolerance to and persistence of BVDV in PI animals have not been elucidated [1-3]. This in vivo study provides not only a unique perspective on the development of immunotolerance to BVDV in PI fetuses, but contributes to our understanding the development of the bovine fetal immune system.