Effects of HIV‐1 gp120 and Protease Inhibitors on Apoptotic Susceptibility of CD34+ Hematopoietic Progenitor Cells

Although CD34+ cells are generally resistant to HIV‐1 infection, direct cytotoxic interactions with HIV‐1 viral proteins can deplete CD34+ cell number through the induction of apoptosis. Treatment with protease inhibitors (PI), a component of many antiretroviral therapy (ART) regimens, may have anti‐apoptotic effects on CD34+ cells. We evaluated whether the HIV‐1 envelope glycoprotein gp120 and PIs affect CD34+ cell apoptotic susceptibility. CD34+ cells were treated with physiological concentrations of: HIV‐1 gp120Bal (R5; 100 ng/mL); HIV‐1 gp120Lav (X4; 100 ng/mL); ritonavir (RTV; 1 μg/mL); atazanavir (ATV; 5.2 μg/mL); or lopinavir (LPV; 9.8 μg/mL), for 48 hours. Apoptosis was induced by staurosporine (1 μmol/L for 3 h) and intracellular levels of active caspase‐3 were determined. Staurosporine‐stimulated active caspase‐3 concentrations were ~65% higher (P<0.05) in cells treated with either gp120 R5 (6.0±0.4 ng/mL) or X4 (6.0±0.1 ng/mL) and ~40% higher (P<0.05) in cells treated with ATV (4.9±0.7 ng/mL) and LPV (5.1±0.2 ng/mL) than control (3.6±0.4 ng/mL). In contrast, RTV (4.1±0.5 ng/mL) did not significantly alter caspase‐3 concentrations. In conclusion, gp120 (R5 or X4), ATV and LPV increase apoptotic susceptibility of CD34+ cells. Reduced resistance of CD34+ cells to apoptosis may contribute to immunological disturbances and cardiovascular dysfunction with HIV‐1 infection.