EFFECTS OF CONGENITAL INFECTION OF SHEEP WITH BORDER DISEASE VIRUS ONMYELIN PROTEINS

Border disease (BD) of sheep is caused by a virus in the genus Pestivi rus that results in decreased myelination throughout the CNS when acqu ired congenitally. Pregnant ewes were inoculated with BD virus at 50 d ays of gestation, and myelin proteins were quantified in several regio ns of the CNS during prenatal and postnatal development of infected la mbs for comparison with age-matched controls. Newborn field-infected l ambs were also examined. Myelin basic protein (MBP), proteolipid prote in (PLP), myelin-associated glycoprotein (MAG), and 2',3'-cyclic nucle otide 3'-phosphodiesterase (CNP) were measured by densitometric scanni ng of western blots. Deficiencies in the myelin proteins were detected as early as 116 days of gestation, and the deficiencies of myelin pro teins were most pronounced in the cerebellum at all ages examined. PLP and MBP increased from 10-30% of normal in cerebellar white matter at birth to 40-60% of normal at 6 months, suggesting some catch-up in th e amount of compact myelin with development. MAG and CNP were between 70 and 80% of control levels in the cerebellum at birth and at 6 month s. Similar results were obtained for the corpus callosum and spinal co rd of infected lambs, but the deficiencies of myelin proteins were not as great. A common finding in all regions examined was that MBP and P LP were reduced more than MAG and CNP. This is probably explained by a greater deficit of compact myelin, in which MBP and PLP are localized , than of associated oligodendroglial membranes, in which MAG and CNP are concentrated, Similar results have been obtained in several dysmye linating mutants, pointing to common factors in virally and geneticall y caused hypomyelination.