Reduction of Human Immunodeficiency Virus Production and Cytopathic Effects by Inhibitors of the Na+/K+/2Cl−Cotransporter

Infection of CD4+T-lymphoblastoid cells by cytopathic strains of HIV-1 results in an increase in cell volume that leads to lysis and cell death. The increase in volume is attributable in part to an HIV-induced increase in intracellular monovalent ion concentrations mediated by the plasma membrane-associated Na+/K+/2 Cl−cotransporter. Loop diuretics, which inhibit cotransporter activity, blocked HIV-induced HIV production and cytopathic effects at physiologically employed concentrations.