Studies of Ruminant Pestivirus Fetopathogenicity With Special Reference to the Nervous System

Jeffrey, Martin (1988) Studies of Ruminant Pestivirus Fetopathogenicity With Special Reference to the Nervous System. Doctor of Veterinary Medicine thesis, University of Glasgow.

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This thesis presents morphologic studies of naturally acquired Bovine virus diarrhoea-mucosal disease (BVD-MD) virus infections of cattle and naturally acquired and experimental Border disease (BD) virus infection of sheep. The distribution and cellular localisaton of selected immunohistochemical central nervous system glial cell markers is described for the normal sheep. Using two of these markers and a monoclonal antibody to BVD-MD virus a double iramunoenzyme labelling technique was used to determine the cellular localisation of BD virus for the persistently viraemic fetal and neonatal sheep. The ultrastructural features of the peripheral nervous system (second muscular branch of sciatic nerve) of a viraemic fetus and neonate is also described. Field studies of BVD-MD virus infection and BD virus infection showed that lesions of hydranencephaly, porencephaly, cerebellar dysplasia and atrophy, and retinopathy occur following pestivirus infections of both cattle and sheep. The infection status (presence of virus or serum neutralising antibody) of affected animals suggests a relationship between the gestational age of infection and the nature of lesions. Animals infected early in gestation are viraemic and show either no significant histopathological changes or, mild retinopathy and/or mild granuloprival cerebellar dysplasia. These lesions are probably caused by virus induced degeneration of proliferating neuroblasts. Viraemic sheep may also show central nervous system hypomyelinogenesis (classical BD). Ultrastructural observations suggest that a deficiency of myelin may also be a feature of the peripheral nervous system of newborn lambs persistently infected with BD virus. Animals with cystic cerebral or cerebellar cavitation are infected around midgestation and are invariably non-viraemic, most show a serological response. One experimentally infected lamb with porencephaly was shown to have viral persistence in white matter of the central nervous system but virus was not demonstrated in viscera or blood. These features suggest that cavitating lesions of the central nervous system following pestivirus infection may have an immunological basis. Immunohistochemical markers of glial cells are widely used in neurobiology generally and have been particularly useful in elucidating glial cell differentiation pathways. Such markers are potentially useful for studies of the effect of pestivirus on the developing central nervous system. The results of experimental immunoperoxidase studies of selected glial cell markers show that glial fibrillary acidic protein, carbonic anhydrase II, myelin basic protein and galactocerebroside are conserved in the sheep. Glial fibrillary acidic protein is expressed in cells which were defined by topography and morphology as protoplasmic astrocytes, fibrous astrocytes, Bergmann glial cells, a sub-population of ependymal cells (including possibly tanycytes), amphicytes of spinal ganglia and some Schwann cells. In the 90 day ovine fetus glial fibrillary acidic protein expression was also seen in sub-pial glia. The processes of some of these cells were continuous with myelin basic protein expressing myelin sheaths. Such cells are morphologically and biochemically similar to transitional cells. In the neonatal lamb brain myelin basic protein is expressed in myelin sheaths and in the cytoplasm of presumed myelinating oligodendroglia. These cells are found throughout the neuraxis and in all funiculi of the spinal cord. Myelin basic protein expression, as determined by the immunoperoxidase method, was found to be a more precise and sensitive method of demonstrating initial stages of myelination than conventional histological stains. However, this method offered no advantage over tinctorial methods for examination of the subsequent advancement of myelination towards maturity. Galactocerebroside expression was seen on frozen sections of spinal cord in populations of subpial glial cells but it was not demonstrated in fixed, paraffin wax embedded tissues. Carbonic anhydrase II was expressed in choroid plexus epithelium and in glial cells of white matter. Double immunoenzyme labelling showed that these latter cells also expressed glial fibrillary acidic protein and were thus identified as fibrous astrocytes. Using monoclonal antibodies raised to BVD-MD virus the immunoperoxi-ase method demonstrated widespread neuronal, glial cell and ependymal cell infection of the spinal cord of fetal and newborn lambs. Cells within the peripheral nervous system were also infected. Double iramunoenzyme labelling showed that glial fibrillary acidic protein expressing cells and myelin basic protein expressing cells were infected with virus. On morphological and biochemical characteristics the infected cells were identified as astrocytes, oligodendrocytes and transitional cells. Morphometric studies of glial fibrill-expressing cells and ary acidic protein expressing cells and myelin basic protein expressing cells show an astrocytosis and a deficiency of myelinating oligodendroglia in the 90 day fetus. These results suggest that myelin deficiency of BD is caused by defective differentiation of oligodendroglia or oligodendro-glial precursor cells.

Item Type: Thesis (Doctor of Veterinary Medicine)
Qualification Level: Doctoral
Keywords: Veterinary science, Animal diseases
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77786
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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