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Science 3 August 1990:
Vol. 249. no. 4968, pp. 549 - 553
DOI: 10.1126/science.2200125
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Articles

Science, Vol 249, Issue 4968, 549-553
Copyright © 1990 by American Association for the Advancement of Science

articles

Specific tropism of HIV-1 for microglial cells in primary human brain cultures

BA Watkins, HH Dorn, WB Kelly, RC Armstrong, BJ Potts, F Michaels, CV Kufta, and M Dubois-Dalcq

Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Human immunodeficiency virus (HIV) frequently causes neurological dysfunction and is abundantly expressed in the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients with HIV encephalitis or myelopathy. The virus is found mostly in cells of the monocyte-macrophage lineage within the CNS, but the possibility of infection of other glial cells has been raised. Therefore, the effects of different HIV-1 and HIV-2 strains were studied in primary cultures of adult human brain containing microglial cells, the resident CNS macrophages, and astrocytes. These cultures could be productively infected with macrophage-adapted HIV-1 isolates but not with T lymphocyte-adapted HIV-1 isolates or two HIV-2 isolates. As determined with a triple-label procedure, primary astrocytes did not express HIV gag antigens and remained normal throughout the 3-week course of infection. In contrast, virus replicated in neighboring microglial cells, often leading to their cell fusion and death. The death of microglial cells, which normally serve immune functions in the CNS, may be a key factor in the pathogenesis of AIDS encephalitis or myelopathy.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)