HIV-1 expression protects macrophages and microglia from apoptotic death.
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.
Cosenza
M A
MA
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Zhao
M-L
ML
Lee
S C
SC
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000821:virology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000473:pathology / Q000821:virology*; D008297:Male; D017628:Microglia / Q000473:pathology / Q000821:virology*; D008875:Middle Aged; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053148:Caspase 3; D020169:Caspases; D016655:HIV Core Protein p24; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C505407:CASP3 protein, human