HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF T-LYMPHOBLASTOID CELLS REDUCES INTRACELLULAR PH

Alterations in plasma membrane function are induced by many cytopathic viruses, including human immunodeficiency virus type 1 (HIV-1). These alterations can result in changes in the intracellular content of ion s and other small molecules and can contribute to cytolysis and death of the infected cell. The pH-sensitive fluorescent probe carboxyethyl) -5,6-carboxyfluorescein-acetoxymethyl ester was used to quantitate int racellular pH (pH(i)) in HIV-1-infected T cells, Infection of cells fr om the CD4(+) T-lymphoblastoid line HUT-78 (RH9 subclone) with HIV-1 s train LAI resulted in a significant decrease of pH(i), from approximat ely 7.2 in mock-infected cells to below 6.7 by day 4 after infection, when cells were undergoing acute cytopathic effects, The pH(i) in pers istently infected cells that survived the acute cytopathic effects of HIV-1 was approximately 6.8 to 7.0, Studies with amiloride, an inhibit or of the Na+/H+ exchange system, suggest that HIV-1-induced intracell ular acidification in lymphocytes is due, in part, to dysfunction of t his plasma membrane ion transport system, The alterations in pH(i) may mediate certain cytopathic effects of HIV-1, thereby contributing to depletion of CD4(+) T lymphocytes in patients with AIDS.