Stimulation of HIV expression by intracellular calcium pump inhibition.
We have studied the role of intracellular calcium sequestration on human immunodeficiency virus (HIV) production by latently infected T-lymphocytic cells. Inhibition of the sarco-endoplasmic reticulum-type calcium transport ATPases by thapsigargin or cyclopiazonic acid induced activation of HIV production in the CEM-derived ACH-2 cells. An approximately 50% depletion of the thapsigargin-sensitive calcium pools as measured fluorimetrically of Indo-loaded cells fully activated virus production. Viral activation was manifest by increases in soluble viral core p24 production, increases in cellular immunofluorescent staining for viral antigens, and increased viral transcription as measured by HIV long terminal repeat-directed expression of the chloramphenicol acetyltransferase reporter gene. Virus induction could be blocked in a dose-dependent manner by the calcium channel blocker econazole. Virus production by the Jurkat-derived HIV-1-inducible J1.1 cells was not significantly stimulated by thapsigargin. These data indicate that intracellular calcium pool function is involved in the control of the transcription of proviral HIV in a cell type-specific manner within the T-lymphoid lineage and that ACH-2 cells represent a useful model for the study of calcium dependent activation of the transcription of proviral HIV.
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Hematology-Oncology Research Laboratory, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
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D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000502:physiology*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014779:Virus Replication / Q000187:drug effects
D006873:Hydroquinones; D007211:Indoles; D013729:Terpenes; C019359:2,5-di-tert-butylhydroquinone; D019284:Thapsigargin; D015500:Chloramphenicol O-Acetyltransferase; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid