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Science 5 February 1988:
Vol. 239. no. 4840, pp. 586 - 592
DOI: 10.1126/science.3277272

Articles

Science, Vol 239, Issue 4840, 586-592
Copyright © 1988 by American Association for the Advancement of Science


articles

The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex

RW Price, B Brew, J Sidtis, M Rosenblum, AC Scheck, and P Cleary

Department of Neurology, Memorial Hospital, New York, NY 10021.

Infection with human immunodeficiency virus type 1 (HIV-1) is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due partially or wholly to a direct effect of the virus on the brain rather than to opportunistic infection, but its pathogenesis is not well understood. Productive HIV-1 brain infection is detected only in a subset of patients and is confined largely or exclusively to macrophages, microglia, and derivative multinucleated cells that are formed by virus-induced cell fusion. Absence of cytolytic infection of neurons, oligodentrocytes, and astrocytes has focused attention on the possible role of indirect mechanisms of brain dysfunction related to either virus or cell-coded toxins. Delayed development of the AIDS dementia complex, despite both early exposure of the nervous system to HIV-1 and chronic leptomeningeal infection, indicates that although this virus is "neurotropic," it is relatively nonpathogenic for the brain in the absence of immunosuppression. Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.


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CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain.
A. L. Edinger, J. L. Mankowski, B. J. Doranz, B. J. Margulies, B. Lee, J. Rucker, M. Sharron, T. L. Hoffman, J. F. Berson, M. C. Zink, et al. (1997)
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COUP-TF and Sp1 Interact and Cooperate in the Transcriptional Activation of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat in Human Microglial Cells.
O. Rohr, D. Aunis, and E. Schaeffer (1997)
J. Biol. Chem. 272, 31149-31155
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Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy.
D. Lopez-Villegas, R. E. Lenkinski, and I. Frank (1997)
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Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene.
J. He, C. M. deCastro, G. R. Vandenbark, J. Busciglio, and D. Gabuzda (1997)
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In Vivo Evidence for Carrier-Mediated Efflux Transport of 3'-Azido-3'-Deoxythymidine and 2',3'-Dideoxyinosine Across the Blood-Brain Barrier via a Probenecid-Sensitive Transport System.
K. Takasawa, T. Terasaki, H. Suzuki, and Y. Sugiyama (1997)
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gp120-Induced Neurotoxicity in Hippocampal Pyramidal Neuron Cultures: Protective Action of TGF-beta 1.
O. Meucci and R. J. Miller (1996)
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Risk of Human Immunodeficiency Virus Type 1--Related Neurologic Disease in a Cohort of Intravenous Drug Users.
K. Marder, X. Liu, Y. Stern, R. Malouf, G. Dooneief, K. Bell, G. Todak, M. Joseph, S. Sorrell, W. E. Sadr, et al. (1995)
Arch Neurol 52, 1174-1182
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Dementia Associated with the Acquired Immunodeficiency Syndrome.
S. A. Lipton and H. E. Gendelman (1995)
N. Engl. J. Med. 332, 934-940
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W. C. Heindel, T. L. Jernigan, S. L. Archibald, C. L. Achim, E. Masliah, and C. A. Wiley (1994)
Arch Neurol 51, 1129-1135
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Neuropsychological Characterization of the AIDS Dementia Complex and Rationalization of a Test Battery.
P. Maruff, J. Currie, V. Malone, C. McArthur-Jackson, B. Mulhall, and E. Benson (1994)
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M. Maj, P. Satz, R. Janssen, M. Zaudig, F. Starace, L. D'Elia, B. Sughondhabirom, M. Mussa, D. Naber, D. Ndetei, et al. (1994)
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