HIV‐1 expression protects macrophages and microglia from apoptotic death

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Abstract
Macrophages and microglia are the predominant cells infected with HIV‐1 in the brain, yet the effects of productive HIV infection on the fate of these cells are poorly understood. In this study, we tested the hypothesis that HIV‐1 expression influences cell death in infected macrophages and microglial cells. We detected apoptosis by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL) in the cerebral white matter of control and HIV encephalitis (HIVE) brains, and quantitatively analysed apoptotic cells with respect to their location (vessel‐associated vs. parenchymal), CD68 expression, and HIV‐1 p24 expression. There were more vessel‐associated, but not more parenchymal, TUNEL+ cells in HIVE cases as compared to controls. Vessel‐associated TUNEL+ cells were primarily endothelial cells (von Willebrand factor+) or macrophages (CD68+). TUNEL+/CD68+ cells were present in both control and HIVE cases in similar frequencies (2.1 ± 0.7% vs. 1.9 ± 0.7% of total CD68+ populations, respectively). In HIVE, TUNEL+/p24+ cells were 0.4 ± 0.2% of the total p24+ cell population, which was lower than the frequency of TUNEL+/CD68+ cells (1.9 ± 0.7%) in the total CD68+ macrophage population. These results suggest that HIV‐1‐infected macrophages and microglia are resistant to apoptosis, and may contribute to the formation of a central nervous system viral reservoir.

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