Acquired immune deficiency syndrome (AIDS) is characterized by a chronic, progressive depletion of T-lymphocytes bearing the CD4 cell surface marker. Human immunodeficiency virus (HIV), the causative agent of AIDS, is a cytolytic retrovirus which infects CD4+ T-lymphocytes resulting in virus-mediated cytopathic effects (CPE). HIV-induced CPE includes fusion of cells to form multinucleated giant cells or syncytia and the death of single cells due to a 'ballooning degeneration' Quantitation of intracellular volume regulation ions, sodium and potassium, was performed using ion-specific fluorescent probes, fluorescent microscopy, digital image analysis, and fluorescent concentration analysis (FCA). There were observable increases in the intracellular free concentrations of both cations in HIV-infected cells. The activity and expression of the Na+/K+/2C1$-$ cotransporter, a diuretic sensitive ion transporter, increased markedly during acute HIV infection of CD4+ lymphocytes. Inhibition of the cotransporter by diuretics inhibits HIV-mediated CPE supporting a critical role for this ion transporter in cell killing by HIV. The activity and expression of the Na+/K+ ATPase (sodium pump), a ouabain-sensitive electrogenic ion transporting enzyme, is reduced early in acute infection and in chronically HIV-infected cells as measured by ouabain binding, western immunoblotting, and binding of $\gamma-\sp{32}$P from ATP. The loss of this critical physiology regulator may be important in CD4+ cell depletion which characterizes HIV infection
