Genetic disorders of myelin make it possible to study the steps in myelinogenesis. An area important to these studies is that of virus induced hypomyelination. This program focuses on studying events that regulate oligodendrocyte differentiation by the use of the pestivirus, border disease (BD) virus in congenitally infected fetal sheep CNS and in a differentiating neural cell culture system. This program also focuses on the comparative study of myelin dysgenesis disorders in humans and in animal models. To investigate in vitro cell tropism of BD virus, primary cultures derived from fetal and adult ovine CNS and PNS were inoculated with BD virus. Infection of all the major cell types represented in these cultures, including oligodendrocytes, astrocytes, fibroblasts, dorsal root ganglion neurons and Schwann cells were found. Oligodendrocyte infection differed only in that these cells were infected earlier and appeared to remain infected longer than astrocytes and fibroblasts. These studies suggest that the selective dysfunction of the oligodendrocyte in BD is not based on a selective viral tropism. Although no human pestivirus has been reported, the malformations of congenital BD and a related virus, bovine viral diarrhea (BVD) virus resemble certain human malformations of unknown etiology. Therefore, we sought evidence for infection with these viruses in high risk mothers. The defect microcephaly was chosen for study because it is a frequent feature of congenital BD and BVD virus infection in animals. We did a serological investigation of 129 mothers who had given birth to children with microcephaly and a similar number of controls. Two mothers with microcephalic infants had antibody to BD and BVD virus. No antibody was detected in controls. This preliminary study suggest that a virus which cross- reacts with animal pestiviruses, possibly a human pestivirus, may exist and be involved in human congenital brain injury.
