Pathologic alterations of blood vessels are a common finding in the brains of children who have died with infection due to the retrovirus, called HIV, which causes the acquired immunodeficiency syndrome (AIDS). Many of these children have had clinical evidence of a progressive neurological disorder, and there is substantial evidence to implicate HIV directly in this encephalopathy. The present research protocol is designed to determine the role of HIV in the pathogenesis of vascular abnormalities in the central nervous system (CNS) of affected children, using several complementary techniques: immunocytochemistry, to localize HIV antigens and to identify affected cell types, with particular reference to cells associated with blood vessels; in situ hybridization, to determine the location of HIV genome; and transmission electron microscopy, to identify the relationship of viral particles to blood vessels and to further characterize affected cell types. Attention will also be directed to the choroid plexus and subependymal vessels, to determine the route of entry of HIV into both the cerebrospinal fluid and the brain, as well as to any alterations in blood-brain barrier which might occur as a consequence of HIV infection. The same techniques will be used in a comparative parallel study of encephalitis in juvenile rhesus monkeys due to the related retrovirus STLV-III. This animal model will also allow more comprehensive study of the time course of CNS infection due to HIV as well as of alterations in the blood-brain barrier. Information gained from this study will be useful in devising therapeutic strategies for this devastating CNS disorder.
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