The neuropathogenicity of two retroviruses was investigated. The human immunodeficiency virus, in addition to its profound effect on the immune system, also causes degenerative changes in the brain, the spinal cord and peripheral nerves. In order to elucidate how it affects the nervous system, transgenic mice were generated that express the entire HIV genome in neurons in the anterior thalamus and in the anterior horn of the spinal cord, and examined clinically, neuropsychologically, electrophysiologically and histologically. Animals developed a neurological syndrome characterized by hypoactivity and weakness, and by axonal degeneration in peripheral nerves. These results provide evidence for a role of HIV in affecting both the central and peripheral nervous systems. / In a second project, pathological effects associated with a disease determining region contained in the gp70 envelope protein of the Cas-Br-E murine leukemia virus, were investigated. In infected mice, this virus causes hind limb paralysis and a spongiform myeloencephalopathy with gliosis and neuronal loss. Stably transfected fibroblasts that express gp70 were injected into the brains of mice, and the animals were examined for histopathological changes attributable to the effects of gp70. While gp70 protein was detected at the implantation site, this was not accompanied by any specific histological changes. These data suggest that the intracerebral expression of the neuropathogenic gp70 protein alone is not sufficient to cause disease, and lend indirect support to a model according to which gp70 causes disease by altering the cytokine profile of infected mononuclear cells in the central nervous system.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.39882 |
| Date | January 1995 |
| Creators | Thomas, Kurt Florian Patrick |
| Contributors | Jolicoeur, Paul (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001467454, proquestno: NN08161, Theses scanned by UMI/ProQuest. |
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