PMID- 8202539 OWN - NLM STAT- MEDLINE DCOM- 19940706 LR - 20191210 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 91 IP - 12 DP - 1994 Jun 7 TI - A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter. PG - 5632-6 AB - 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. FAU - Lee, M O AU - Lee MO AD - Cancer Center, La Jolla Cancer Research Foundation, CA 92037. FAU - Hobbs, P D AU - Hobbs PD FAU - Zhang, X K AU - Zhang XK FAU - Dawson, M I AU - Dawson MI FAU - Pfahl, M AU - Pfahl M LA - eng GR - CA50676/CA/NCI NIH HHS/United States GR - CA60988/CA/NCI NIH HHS/United States GR - P01 CA51993/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoids) RN - 9006-59-1 (Ovalbumin) SB - IM EIN - Proc Natl Acad Sci U S A 1994 Nov 22;91(24):11767 MH - Animals MH - Base Sequence MH - Cell Line MH - Chlorocebus aethiops MH - Gene Expression Regulation, Viral/*drug effects MH - HIV Long Terminal Repeat/*genetics MH - HIV-1/*genetics MH - Molecular Sequence Data MH - Ovalbumin/genetics MH - *Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - Receptors, Retinoic Acid/*antagonists & inhibitors MH - Retinoids/*pharmacology MH - Virus Replication/drug effects PMC - PMC44050 EDAT- 1994/06/07 00:00 MHDA- 1994/06/07 00:01 PMCR- 1994/12/07 CRDT- 1994/06/07 00:00 PHST- 1994/06/07 00:00 [pubmed] PHST- 1994/06/07 00:01 [medline] PHST- 1994/06/07 00:00 [entrez] PHST- 1994/12/07 00:00 [pmc-release] AID - 10.1073/pnas.91.12.5632 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5632-6. doi: 10.1073/pnas.91.12.5632.