VARIATION IN NEUROPATHOGENICITY IN SHEEP FETUSES TRANSPLACENTALLY INFECTED WITH NONCYTOPATHOGENIC AND CYTOPATHOGENIC BIOTYPES OF BOVINE-VIRUS DIARRHEA VIRUS

Pregnant Merino ewes were inoculated intravenously between days 63 and 65 of gestation with a non-cytopathogenic (ncp) bovine-virus diarrhoe a-virus (BVDV) isolate (experiment A). The histomorphological findings and the distribution of viral antigen, as revealed by immunohistochem istry in brains of fetuses from experiment A, were compared with those seen in fetal brains from a previous study (experiment B); in which p regnant ewes had been intravenously infected between days 65 and 68 of gestation with the cytopathogenic (cp) BVDV strain Indiana. The two v iruses showed remarkable variations concerning their pathogenicity for the developing fetal brain. The cp BVDV had a much higher neuropathog enic potential than the ncp BVDV and induced severe intracranial malfo rmations in most fetuses. In experiment A, exclusively relatively mild leucoencephalomalacic lesions occurred. Between fetuses of the two ex periments, significant differences concerning the distribution of vira l antigen and the inflammatory response were found. In the majority of fetal brains from experiment B examined at days 10, 14 and 21 post in oculation (p.i.), antigen-containing differentiated brain cells (neuro ns, astrocytes, oligodendrocytes) and undifferentiated cells in the pe riventricular germinal zones were seen throughout the different zones of the developing telencephalon and cerebellum. At 21 days p.i., a mar ked inflammatory response consisting of brain macrophages and other mo nonuclear cells occurred in the meninges and in the brain parenchyma o f fetuses from experiment B. In brain sections of fetuses infected wit h ncp BVDV, in contrast to fetuses infected with cp BVDV, viral antige n was not detectable during the early stages (days 10 and 20) p.i., an d histopathological lesions were nor seen at this stage. Ar days 41 an d 47 p.i., antigen-positive astrocytes and oligodendrocytes were found in the developing white matter of the telencephalon and cerebellum. F urthermore, antigen-containing neurons a ere seen in the developing ce rebral cortex. Cellular infiltrations in fetal brains from experiment A were limited to the leucoencephalomalacic areas in the developing ce rebral and cerebellar white matter and consisted exclusively of brain macrophages. Immunohistochemical staining in brain sections of fetuses from both experiments revealed chat numerous perivascular cells conta ined viral antigen, whilst positive endothelial cells were exclusively found in fetuses from experiment A. From the findings of this study i t was concluded that the cp BVDV stain used ill experiment B has a mar ked tropism for the fecal brain and both its already differentiated an d undifferentiated cell populations, and that the resulting brain lesi ons primarily are the consequence of a direct cytolysis of these cells . The possible role of brain macrophages and of endothelial cells for the development of leucoencephalomalacic alterations in fetuses infect ed with ncp virus is discussed.