Effect of the calcium channel blocker verapamil on human immunodeficiency virus type 1 replication in lymphoid cells.
Cell signaling events are known to affect human immunodeficiency virus type 1 (HIV-1) replication. Treatment of lymphoid CEM cells with the calcium channel blocker verapamil (25-75 microM) enhanced HIV-1 expression in acute, whole virus infection experiments, despite lowering intracellular calcium levels, ablating the acute rise in intracellular calcium normally seen with infection, and lengthening the doubling time of cell replication. Verapamil had no effect on cell surface CD4 expression. Transfection of CEM cells with plasmids containing the HIV-1 long terminal repeat linked to the chloramphenicol acetyltransferase reporter gene showed that verapamil enhanced expression of the HIV-1 long terminal repeat in a dose-dependent fashion. This effect was abolished by mutations in the binding sites for nuclear factor kappa-B. Electrophoretic mobility shift assays confirmed that verapamil induced nuclear factor kappa-B activity in CEM cells. Thus, verapamil, in high concentrations, can potentiate HIV-1 replication in lymphoid cells, and this effect may be mediated by induction of nuclear factor kappa-B.
Harbison
M A
MA
Harvard Medical School, Infectious Disease Section, New England Deaconess Hospital, Boston, MA 02215.
Kim
S Y
SY
Gillis
J M
JM
Hammer
S M
SM
D015704:CD4 Antigens / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D016328:NF-kappa B; D014700:Verapamil; D012194:RNA-Directed DNA Polymerase; D002118:Calcium