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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025121-02
Application #
3410265
Study Section
Pathology A Study Section (PTHA)
Project Start
1987-07-01
Project End
1990-12-31
Budget Start
1988-01-01
Budget End
1989-12-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107
Sharer, L R (1994) Neuropathology and pathogenesis of SIV infection of the central nervous system. Res Publ Assoc Res Nerv Ment Dis 72:133-45
Saito, Y; Sharer, L R; Epstein, L G et al. (1994) Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44:474-81
Sharer, L R (1992) Pathology of HIV-1 infection of the central nervous system. A review. J Neuropathol Exp Neurol 51:3-11
Sharer, L R; Michaels, J; Murphey-Corb, M et al. (1991) Serial pathogenesis study of SIV brain infection. J Med Primatol 20:211-7
Sharer, L R; Dowling, P C; Michaels, J et al. (1990) Spinal cord disease in children with HIV-1 infection: a combined molecular biological and neuropathological study. Neuropathol Appl Neurobiol 16:317-31
Sharer, L R; Cho, E S (1989) Neuropathology of HIV infection: adults versus children. Prog AIDS Pathol 1:131-41
Epstein, L G (1989) Lentiviral encephalitides in the immature host: a comparison of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) brain infection. Brain Dev 11:353-9
Michaels, J; Sharer, L R; Epstein, L G (1988) Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review. Immunodefic Rev 1:71-104
Sharer, L R; Baskin, G B; Cho, E S et al. (1988) Comparison of simian immunodeficiency virus and human immunodeficiency virus encephalitides in the immature host. Ann Neurol 23 Suppl:S108-12
Epstein, L G; Sharer, L R; Goudsmit, J (1988) Neurological and neuropathological features of human immunodeficiency virus infection in children. Ann Neurol 23 Suppl:S19-23

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