PATHOGENESIS OF LENTIVIRUS NEUROLOGIC DISEASE

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Neurologic disease is now recognized to be a devastating and frequent consequence of human immunodeficiency virus (HIV) infection. The means of viral entry into the nervous system and the mechanisms of viral damage are unknown. A practical model of lentivirus induced neuorlogical disease would be of great value in the study of these questions. Feline T lymphotropic lentivirus (FTLV) is a newly described feline lentivirus which is immunosuppressive, T lymphotrophic, and on the basis of preliminary data described below appears to be neurovirulent. The aims of this proposal are: (1) to further define the neurovirulence, 2) to determine the peripheral cells and tissue replicating FTLV and the means of spread of the virus to the nervous system, and 3) the molecular characterization of the virus and its expression in relevant cells and tissues. The nature and extent of viral induced neural damage will be studied by analysis of feline tissues from all levels of the nervous systems, from cortex to peripheral nerve, at intervals following intracranial or peripheral virus inoculation. The extent and distribution of viral replication will be determined using immunocytochemistry with rabbit antiviral antibody and in situ hybridization with nucleic acid probes. The cells involved in the inflammatory response will be identified, and the identity of infected inflammatory and neural cells determined. The intergrity of myelin and the structural and biochemical nature of any defects in myelination will be studied. Viral replication will be studied in vitro in relevant primary cell lines of the natural host. The virus will be cloned to provide adequate molecular probes for virus localization and determination of the state of viral gene expression within the nervous system, and ultimately to allow study of the genomic structure gene expression and regulation of FTLV.