The Fetal Brain in Bovine Viral Diarrhea Virus-infected Calves: Lesions, Distribution, and Cellular Heterogeneity of Viral Antigen at 190 Days Gestation

Abstract

Previous studies have shown that the brain is a target of persistent infection with bovine viral diarrhea virus (BVDV) and have demonstrated viral tropism for neurons as well as other endogenous cell types in diverse brain areas. Apart from foci of mild residual inflammation in some postnatal calves, consistent brain lesions, per se, have not been reported. No similar comprehensive studies of the brain have been reported in bovine fetuses. In the current study, 12 BVDV-seronegative heifers were inoculated intranasally with a 2-ml 4.4 log(10) TCID(50)/ml dose of noncytopathic type 2 BVDV at 75 and 175 days of gestation to create persistently and transiently infected fetuses, respectively. In only persistently infected fetuses, encephaloclastic lesions resulting in pseudocysts were observed in the subependymal zone in the region of the median eminence and adjacent corona radiata as well as in the region of the external capsule associated with lenticulostriate arteries. Additionally, areas of rarefaction in white matter were observed at the tips of cerebrocortical gyri and in the external capsule. The distribution of viral antigen was examined by immunohistochemical labeling using the 15C5 anti-BVDV monoclonal antibody. Viral antigen was detected only in calves inoculated at 75 days of gestation, i.e., persistently infected. The pattern of BVDV immunolabeling revealed both similarities and differences compared with previous studies in postnatal calves, suggesting that viral infection in the brain is a dynamic and progressive rather than static process.