STIMULATION OF HIV EXPRESSION BY INTRACELLULAR CALCIUM-PUMP INHIBITION

We have studied the role of intracellular calcium sequestration on hum an immunodeficiency virus (HIV) production by latently infected T-lymp hocytic cells. Inhibition of the sarco-endoplasmic reticulum-type calc ium transport ATPases by thapsigargin or cyclopiazonic acid induced ac tivation of HIV production in the GEM-derived ACH-S cells. An approxim ately 50% depletion of the thapsigargin-sensitive calcium pools as mea sured fluorimetrically of Indo-loaded cells fully activated virus prod uction. Viral activation was manifest by increases in soluble viral co re p24 production, increases in cellular immunofluorescent staining fo r viral antigens, and increased viral transcription as measured by HIV long terminal repeat-directed expression of the chloramphenicol acety ltransferase reporter gene. Virus induction could be blocked in a dose dependent manner by the calcium channel blocker econazole. Virus prod uction by the Jurkat-derived HIV-l-inducible J1.1 cells was not signif icantly stimulated by thapsigargin. These data indicate that intracell ular calcium pool function is involved in the control of the transcrip tion of proviral HIV in a cell type-specific manner within the T-Iymph oid lineage and that AGH-2 cells represent a useful model for the stud y of calcium dependent activation of the transcription of proviral HIV .