Fetal Hepatic Response to Bovine Viral Diarrhea Virus Infection in Utero

Non-cytopathic bovine viral diarrhea virus (ncp BVDV) can cause persistent infection (PI) in animals infected in utero during early gestation. PI animals shed the virus for life and are the major source of the virus in herds. The mechanism responsible for BVDV immune tolerance in the PI fetus is unknown. We assessed the impact of BVDV infection on the fetal liver. Dams were inoculated with ncp BVDV at gestational day 75. Fetal liver samples were collected at necropsy, 7 and 14 days post-maternal-BVDV inoculation. BVDV antigen was not detected in the liver at gestational day 82 (7 days post-maternal inoculation). However, at 14 days post-maternal inoculation, BVDV was detected by immunohistochemistry in fetal Kupffer cells. Flow cytometry analysis showed a higher percentage of hepatic immune cells expressed MHC I and MHC II in BVDV-infected fetal liver (as compared to uninfected controls). Immunofluorescence was used to identify Kupffer cells, which were positive for BVDV antigen, near populations of CD3+ lymphocytes. The identification of BVDV in the fetal liver Kupffer cells at 14 days post inoculation is interesting in the context of establishment of tolerance in persistent infection. These data indicate the presence of a hepatic immune response to fetal infection.