Human renal biopsy studies suggest the presence of HIV-1 and associated signs of injury in renal tubular epithelial cells. Because renal epithelial cells lack conventional HIV-1 receptors, the modus operandi of HIV-1 in the induction of tubular cell injury remains a mystery. In the present study, we evaluated the role of HIV-1 gene expression in human proximal tubular cell apoptosis and cell cycle progression. HIV-1- or vector-transduced cells were assayed for cellular injury and cell cycle defect. HIV-1-transduced cells showed the progressive loss of viability in a time-dependent manner. Similarly, HIV-1-transduced cells showed greater apoptosis when compared with vector-transduced cells. A higher number of HIV-1 expressing cells showed cell cycle arrest at G2/M phase and enhanced tubular cell expression of phospho-p53(ser15), phospho-cdc-2(Tyr 15), and phospho-chk-2 (Thr 68). These findings suggest that in addition to the activation of apoptotic pathway, HIV-1-induced G2/M arrest may also contribute to tubular cell injury.