GSBS Student Publications


Synergistic activation of simian immunodeficiency virus and human immunodeficiency virus type 1 transcription by retinoic acid and phorbol ester through an NF-kappa B-independent mechanism

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Immunology and Virology; Program in Molecular Medicine



Document Type


Medical Subject Headings

Base Sequence; Binding Sites; Cell Line; Drug Synergism; Gene Expression Regulation, Viral; Genes, fos; HIV-1; Humans; Lymphoma, Large B-Cell, Diffuse; Molecular Sequence Data; NF-kappa B; Oligodeoxyribonucleotides; Plasmids; RNA, Messenger; RNA, Viral; Repetitive Sequences, Nucleic Acid; Simian immunodeficiency virus; TATA Box; Tetradecanoylphorbol Acetate; Transcription Factors; Transcription, Genetic; Tretinoin; Tumor Cells, Cultured


Life Sciences | Medicine and Health Sciences


The activation of human immunodeficiency virus type 1 (HIV-1) expression in latently infected cells by exogenous agents is believed to be important in the progression of AIDS. Most factors that are known to activate HIV-1 gene expression increase the binding of NF-kappa B or NF-kappa B-like transcription factors to the HIV-1 core enhancer region. In this report, we demonstrate that retinoic acid (RA) treatment of promonocytic U937 cells stimulates expression from the simian immunodeficiency virus (SIVmac) long terminal repeat (LTR). Furthermore, RA and phorbol 12-myristate 13-acetate (PMA) synergistically stimulated both SIVmac and HIV-1 LTRs to levels of expression comparable to that achieved by the viral transactivator Tat. The cis-acting elements required for a response to RA and PMA cotreatment are located between nucleotides -50 and +1 of SIVmac and between nucleotides -83 and +80 of HIV-1. Thus, the synergistic stimulation induced by RA and PMA is NF-kappa B independent. Analysis of deletion mutants of the SIVmac LTR demonstrates that RA and PMA stimulation cooperates with NF-kappa B and Sp1. An SIVmac LTR-reporter gene construct [pLTR(-50/+466)CAT] lacking NF-kappa B and Sp1 binding sites was not activated by Tat in untreated cells but was activated in cells that were cotreated with RA and PMA. Furthermore, gel retardation assays demonstrated that RA treatment causes a change in the pattern of a cellular factor(s) which binds to the -50 through +1 region of the SIVmac LTR. These data suggest that RA induces a PMA-activatable cellular factor that cooperates with NF-kappa B, Sp1, or Tat to stimulate LTR-directed transcription.

Rights and Permissions

Citation: J Virol. 1994 Oct;68(10):6598-604.

Related Resources

Link to article in PubMed

Journal Title

Journal of virology

PubMed ID