HIV-1 expression protects macrophages and microglia from apoptotic death

Neuropathol Appl Neurobiol. 2004 Oct;30(5):478-90. doi: 10.1111/j.1365-2990.2004.00563.x.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / metabolism
  • AIDS Dementia Complex / pathology*
  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Apoptosis / physiology*
  • Brain / pathology
  • Brain / virology
  • Caspase 3
  • Caspases / metabolism
  • Endothelial Cells / metabolism
  • Endothelial Cells / virology
  • Female
  • HIV Core Protein p24 / biosynthesis
  • HIV Infections / metabolism
  • HIV Infections / pathology*
  • HIV-1
  • Humans
  • In Situ Nick-End Labeling
  • Macrophages / pathology
  • Macrophages / virology*
  • Male
  • Microglia / pathology
  • Microglia / virology*
  • Middle Aged

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • HIV Core Protein p24
  • CASP3 protein, human
  • Caspase 3
  • Caspases