Effect of tamoxifen on regulation of viral replication and human
immunodeficiency virus (HIV) long terminal repeat-directed transcription in
cells chronically infected with HIV-1
J Laurence, H Cooke and SK Sikder
Laboratory for AIDS Virus Research, New York Hospital, NY.
The protein kinase C (PKC) activator phorbol myristate acetate (PMA) was
used to upregulate viral replication in a clone of promonocytic cells
chronically infected with human immunodeficiency virus (HIV)-1. Induction
of virus could be inhibited by the triphenylethylene anti- estrogen
tamoxifen at concentrations that had minimal effects on cellular DNA
synthetic responses and cell cycle kinetics. This effect correlated with
tamoxifen's ability to block PMA-mediated enhancement of
HIV-promoter-driven transactivation in cells of monocyte and CD4+ T-
lymphocyte lineages. No interference with a primary infection was noted.
Tamoxifen's mechanism of action may relate both to its capacity to inhibit
PKC and to consensus sequences for gonadal steroid responsive elements in
the HIV long terminal repeat, as it was able to partially inhibit another
HIV activator, 5-azacytidine, which does not modulate PKC function. The
finding that regulation of HIV in a model for low-level chronic or latent
infection is amenable to a nonimmunosuppressive steroid antagonist may
suggest approaches to pharmacologic intervention early in HIV infection.
Volume 75,
Issue 3,
pp. 696-703,
02/01/1990
Copyright © 1990 by The American Society of Hematology
