2018 Summer.Includes bibliographical references.Bovine viral diarrhea virus (BVDV) infection of bovine fetuses in the first 125 days of pregnancy results in persistently infected (PI) cattle and transiently infected (TI) cattle become infected, but have a developed immune system enabling them to clear the virus. PI cattle are the main source of BVDV infection in populations causing significant economic losses to the industry worldwide. The mechanisms that lead to this "immunotolerant" state are not well defined. Following maternal inoculation with BVDV on day 75 of gestation, fetal infection was determined by presence of viral mRNA. Fetal infection occurred by day 89 of gestation with a peak at day 97 and a significant 10-fold decrease in viral titer at days 192 and 245 of gestation. BVDV was never completely eliminated in the fetus and persisted at lower, but significant levels. We hypothesized that there is dysgenesis of the fetal thymus, inhibiting functional innate and adaptive immune responses following maternal infection with BVDV. Total RNA was extracted from the thymus of uninfected control and BVDV-infected fetuses at days 89, 97, 190, and 245 of gestation. Genes representing the innate immune system, T and B cell receptor signaling, and the antigen processing and presentation in both the MHC I and MHC II pathways were explored using RT-qPCR. There were significant increases (P ≤ 0.05) observed in all innate genes analyzed (RIG-I, IRF7, NF-kB, IFNβ, and ISG15) in TI fetuses, with minimal responses in PI fetuses. There were significant decreases (P ≤ 0.05) of antigen presentation genes and adaptive immune system genes LMP2, TAP1, β2M, CD8a, CD8b, CIITA, CD4, IFI16, CXCL16, CXCR6, and CD79b in day 190 PI fetuses. Persistent BVDV infection may initiate fetal adaptive immune responses, which are not fully activated over time because of "immunotolerance" caused by impaired antigen processing. Longer-term consequences of fetal PI remain to be determined in context of postnatal impaired immune responses to secondary infections
