685 Ethanol Strongly Potentiates Apoptosis Induced by HIV-1 Proteins in Primary Human Brain Microvascular Endothelial Cells E. Acheampong*1, M. Mukhtar1, Z. Parveen1, N. Ngoubilly1, N. Ahmad2, C. Patel1, R. Pomerantz1 1Thomas Jefferson Univ, Philadelphia, PA and 2Univ of Pennsylvania, Philadelphia
Background: Ethanol may have significant effects on human immunodeficiency virus type I (HIV-1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied on the pro-apoptotic potential of various HIV-1 proteins in primary isolated human brain microvascular endothelial cells (MVECs), a major cellular component of the blood-brain barrier (BBB).
Methods: Low passage primary brain MVECs were treated with recombinant HIV-1 proteins Nef, Vpr, Tat, and gp120 proteins from X4, R5, and X4R5 viral strains, with and without ethanol at various physiologically relevant concentrations. The apoptotic potential of each HIV-1 protein with and without ethanol was compared with cells treated with ethanol alone or GST protein as a control under similar conditions.
Results: Specific HIV-1 proteins induced apoptosis in primary isolated human brain MVECs, which was potentiated by treatment with 0.1% and 0.3% vol/vol of ethanol. Co-treatment with ethanol and specific HIV-1 proteins showed enhanced lactate dehydrogenase (LDH) release, as compared with MVECs treated with ethanol alone. The presence of ethanol in in vitro culture medium also enhanced HIV-1 protein-mediated tumor necrosis factor-alpha (TNF-a) production, as compared with cells treated with ethanol alone or GST protein.
Conclusion: These studies demonstrate ethanol’s potential for inducing apoptosis of primary isolated human brain MVECs with relevant HIV-1-specific proteins, and suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and neuropathogenesis in vivo.
