Epidemiologic and virologic data strongly suggest that the acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). Immunopathologic evidence suggests that HIV might directly or indirectly or cause inflammation and destruction of central nervous system (CNS) tissue as seen in AIDS encephalitis (meningoencephalomyelitis). This disease is characterized by destruction of white matter and the presence of many perivascular or parenchymal monocyte- macrohages, including multinucleated giant cells. A small component of AIDS encephalitis is observed in most HIV-positive patients, and severe dementia is frequently found in AIDS patients. CNS autopsy tissue and cerebrospinal fluid (CSF) will be collected to study the phenotype of CNS parenchymal cells and inflammatory cells in relation to the presence of HIV proteins and nucleic acid. Immunoperoxidase staining of frozen or formalin- fixed, paraffin-embedded sections of CNS with monoclonal antibodies or specific antisera, including double (two antigens as targets) labeling, will be used to identify astrocytes, oligodendrocytes, neurons, vascular endothelial cells, monocyte- macrophages, B lymphocytes, subsets of T lymphocytes, immunoglobulins and other serum proteins, interferon, interleukin-2 and its receptor, major histocompatibility complex antigens (classes I and II) and HIV proteins, which may interact in the development of AIDS encephalitis. In-situ hybridization will be used with an HIV-RNA probe to localize HIV gene copies in single cells in tissue sections, while viral isolation of CSF and tissue will include cell culture for amplification of the virus. Antibodies to HIV in the CSF will be detected by quantitative immunoblotting. Data generated should help in understanding the pathogenesis of AIDS dementia and AIDS encephalitis, conditions very likely caused in part by HIV, opportunistic infection in the CNS, autoallergic encephalitis and vasculitis associated with viral or bacterial systemic infections. The proposed studies should be particularly important for monitoring effects of various chemotherapeutic agents that are currently undergoing clinical trails at our institution.
