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A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter.

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A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhang, X. K. Pfahl, M. Hobbs, P. D. Lee, M. O. Dawson, M. I.
Description	Author Affiliation: Lee MO ( Cancer Center, La Jolla Cancer Research Foundation, CA 92037.);
Abstract	Retinoids regulate a broad range of biological processes and affect cell growth and differentiation of many cell types, including the immune system. Recently, it was reported that human immunodeficiency virus type 1 (HIV-1) expression in macrophages is enhanced by retinoic acid (RA). Retinoid signals are mediated by the RA receptors (RARs) and retinoid X receptors (RXRs) that bind to specific RA responsive elements (RAREs) in the promoter region of susceptible genes. Here, we report on a RARE in the long terminal repeat (LTR) region that allows activation of the HIV-1 LTR. The RARE is composed of two consensus RARE half-sites (A/GGGTCA) arranged as a palindrome separated by 9 nucleotides and is activated by both RAR/RXR heterodimers and RXR homodimers. We show that the COUP (chicken ovalbumin upstream promoter) orphan receptors also bind to the HIV-1 RARE and repress the retinoid response of the HIV-1 RARE or the HIV-1 LTR. Furthermore, a newly discovered synthetic retinoid is shown to be a potent inhibitor of retinoid-induced activation of the HIV-1 RARE. These observations suggest additional approaches for the inhibition of HIV replication.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Expression Regulation, Viral Drug Effects HIV Long Terminal Repeat Genetics HIV-1 Promoter Regions, Genetic Receptors, Retinoic Acid Antagonists & Inhibitors Retinoids Pharmacology Animals Cell Line Cercopithecus Aethiops Molecular Sequence Data Ovalbumin RNA, Messenger Virus Replication Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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