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

Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5632-6. doi: 10.1073/pnas.91.12.5632.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chlorocebus aethiops
  • Gene Expression Regulation, Viral / drug effects*
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / genetics*
  • Molecular Sequence Data
  • Ovalbumin / genetics
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • Receptors, Retinoic Acid / antagonists & inhibitors*
  • Retinoids / pharmacology*
  • Virus Replication / drug effects


  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoids
  • Ovalbumin