Open AccessA synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter.
Author(s) -
MiOck Lee,
Peter D. Hobbs,
Xiaokun Zhang,
Marcia I. Dawson,
Magnus Pfahl
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.12.5632
Subject(s) - retinoid , retinoid x receptor , biology , retinoic acid , retinoid x receptor alpha , long terminal repeat , receptor , microbiology and biotechnology , virology , cell culture , transcription factor , gene , nuclear receptor , genetics , gene expression
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.