Human immunodeficiency virus type 1 Vpr induces apoptosis through caspase activation

Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion. Vpr induces cell cycle arre st at the G(2)/M phase of the cell cycle, and this arrest is followed by ap optosis. We examined the mechanism of Vpr-induced apoptosis and found that HIV-1 Vpr-induced apoptosis requires the activation of a number of cellular cysteinyl aspartate-specific proteases (caspases). We demonstrate that ect opic expression of anti-apoptotic viral proteins, which inhibit caspase act ivity, and addition of synthetic peptides, which represent caspase cleavage sites, can inhibit Vpr-induced apoptosis. Finally, inhibition of caspase a ctivity and subsequent inhibition of apoptosis results in increased viral e xpression, suggesting that therapeutic strategies aimed at reducing Vpr-ind uced apoptosis in vivo require careful consideration.