Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1994 Oct;68(10):6598–6604. doi: 10.1128/jvi.68.10.6598-6604.1994

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.

J W Maciaszek 1, D A Talmage 1, G A Viglianti 1
PMCID: PMC237080  PMID: 8083995

Abstract

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.

Full text

PDF
6598

Images in this article

6599Image
on p.6599
6600Image
on p.6600
6602Image
on p.6602

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  2. Berkenstam A., Vivanco Ruiz M. M., Barettino D., Horikoshi M., Stunnenberg H. G. Cooperativity in transactivation between retinoic acid receptor and TFIID requires an activity analogous to E1A. Cell. 1992 May 1;69(3):401–412. doi: 10.1016/0092-8674(92)90443-g. [DOI] [PubMed] [Google Scholar]
  3. Berkhout B., Gatignol A., Rabson A. B., Jeang K. T. TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. Cell. 1990 Aug 24;62(4):757–767. doi: 10.1016/0092-8674(90)90120-4. [DOI] [PubMed] [Google Scholar]
  4. Berkhout B., Jeang K. T. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1992 Jan;66(1):139–149. doi: 10.1128/jvi.66.1.139-149.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berkhout B., Jeang K. T. trans activation of human immunodeficiency virus type 1 is sequence specific for both the single-stranded bulge and loop of the trans-acting-responsive hairpin: a quantitative analysis. J Virol. 1989 Dec;63(12):5501–5504. doi: 10.1128/jvi.63.12.5501-5504.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Castaigne S., Chomienne C., Daniel M. T., Ballerini P., Berger R., Fenaux P., Degos L. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704–1709. [PubMed] [Google Scholar]
  7. Cullen B. R. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. doi: 10.1016/0092-8674(86)90696-3. [DOI] [PubMed] [Google Scholar]
  8. De Luca L. M. Retinoids and their receptors in differentiation, embryogenesis, and neoplasia. FASEB J. 1991 Nov;5(14):2924–2933. [PubMed] [Google Scholar]
  9. Du H., Roy A. L., Roeder R. G. Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. EMBO J. 1993 Feb;12(2):501–511. doi: 10.1002/j.1460-2075.1993.tb05682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duh E. J., Maury W. J., Folks T. M., Fauci A. S., Rabson A. B. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974–5978. doi: 10.1073/pnas.86.15.5974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gilinger G., Alwine J. C. Transcriptional activation by simian virus 40 large T antigen: requirements for simple promoter structures containing either TATA or initiator elements with variable upstream factor binding sites. J Virol. 1993 Nov;67(11):6682–6688. doi: 10.1128/jvi.67.11.6682-6688.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Griffin G. E., Leung K., Folks T. M., Kunkel S., Nabel G. J. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B. Nature. 1989 May 4;339(6219):70–73. doi: 10.1038/339070a0. [DOI] [PubMed] [Google Scholar]
  14. Gruda M. C., Zabolotny J. M., Xiao J. H., Davidson I., Alwine J. C. Transcriptional activation by simian virus 40 large T antigen: interactions with multiple components of the transcription complex. Mol Cell Biol. 1993 Feb;13(2):961–969. doi: 10.1128/mcb.13.2.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gudas L. J. Retinoids, retinoid-responsive genes, cell differentiation, and cancer. Cell Growth Differ. 1992 Sep;3(9):655–662. [PubMed] [Google Scholar]
  16. Kamine J., Chinnadurai G. Synergistic activation of the human immunodeficiency virus type 1 promoter by the viral Tat protein and cellular transcription factor Sp1. J Virol. 1992 Jun;66(6):3932–3936. doi: 10.1128/jvi.66.6.3932-3936.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kashanchi F., Piras G., Radonovich M. F., Duvall J. F., Fattaey A., Chiang C. M., Roeder R. G., Brady J. N. Direct interaction of human TFIID with the HIV-1 transactivator tat. Nature. 1994 Jan 20;367(6460):295–299. doi: 10.1038/367295a0. [DOI] [PubMed] [Google Scholar]
  18. Kaufman J. D., Valandra G., Roderiquez G., Bushar G., Giri C., Norcross M. A. Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element. Mol Cell Biol. 1987 Oct;7(10):3759–3766. doi: 10.1128/mcb.7.10.3759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keaveney M., Berkenstam A., Feigenbutz M., Vriend G., Stunnenberg H. G. Residues in the TATA-binding protein required to mediate a transcriptional response to retinoic acid in EC cells. Nature. 1993 Oct 7;365(6446):562–566. doi: 10.1038/365562a0. [DOI] [PubMed] [Google Scholar]
  20. Kornfeld H., Riedel N., Viglianti G. A., Hirsch V., Mullins J. I. Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. Nature. 1987 Apr 9;326(6113):610–613. doi: 10.1038/326610a0. [DOI] [PubMed] [Google Scholar]
  21. La Thangue N. B., Rigby P. W. An adenovirus E1A-like transcription factor is regulated during the differentiation of murine embryonal carcinoma stem cells. Cell. 1987 May 22;49(4):507–513. doi: 10.1016/0092-8674(87)90453-3. [DOI] [PubMed] [Google Scholar]
  22. Lie S. O., Wathne K. O., Petersen L. B., Slørdahl S. H., Norum K. R. High-dose retinol in children with acute myelogenous leukemia in remission. Eur J Haematol. 1988 May;40(5):460–465. doi: 10.1111/j.1600-0609.1988.tb00856.x. [DOI] [PubMed] [Google Scholar]
  23. Margolis D. M., Rabson A. B., Straus S. E., Ostrove J. M. Transactivation of the HIV-1 LTR by HSV-1 immediate-early genes. Virology. 1992 Feb;186(2):788–791. doi: 10.1016/0042-6822(92)90048-t. [DOI] [PubMed] [Google Scholar]
  24. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  25. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  26. Nabel G. J., Rice S. A., Knipe D. M., Baltimore D. Alternative mechanisms for activation of human immunodeficiency virus enhancer in T cells. Science. 1988 Mar 11;239(4845):1299–1302. doi: 10.1126/science.2830675. [DOI] [PubMed] [Google Scholar]
  27. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  28. Olsson I. L., Breitman T. R., Gallo R. C. Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3':5'-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor. Cancer Res. 1982 Oct;42(10):3928–3933. [PubMed] [Google Scholar]
  29. Olsson I. L., Breitman T. R. Induction of differentiation of the human histiocytic lymphoma cell line U-937 by retinoic acid and cyclic adenosine 3':5'-monophosphate-inducing agents. Cancer Res. 1982 Oct;42(10):3924–3927. [PubMed] [Google Scholar]
  30. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Parkin N. T., Cohen E. A., Darveau A., Rosen C., Haseltine W., Sonenberg N. Mutational analysis of the 5' non-coding region of human immunodeficiency virus type 1: effects of secondary structure on translation. EMBO J. 1988 Sep;7(9):2831–2837. doi: 10.1002/j.1460-2075.1988.tb03139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Poli G., Fauci A. S. Cytokine modulation of HIV expression. Semin Immunol. 1993 Jun;5(3):165–173. doi: 10.1006/smim.1993.1020. [DOI] [PubMed] [Google Scholar]
  33. Pomerantz R. J., Feinberg M. B., Trono D., Baltimore D. Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. J Exp Med. 1990 Jul 1;172(1):253–261. doi: 10.1084/jem.172.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reddy E. P., Dasgupta P. Regulation of HIV-1 gene expression by cellular transcription factors. Pathobiology. 1992;60(4):219–224. doi: 10.1159/000163726. [DOI] [PubMed] [Google Scholar]
  35. Renjifo B., Speck N. A., Winandy S., Hopkins N., Li Y. cis-acting elements in the U3 region of a simian immunodeficiency virus. J Virol. 1990 Jun;64(6):3130–3134. doi: 10.1128/jvi.64.6.3130-3134.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rice P. W., Cole C. N. Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen. J Virol. 1993 Nov;67(11):6689–6697. doi: 10.1128/jvi.67.11.6689-6697.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  38. Roy S., Delling U., Chen C. H., Rosen C. A., Sonenberg N. A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. Genes Dev. 1990 Aug;4(8):1365–1373. doi: 10.1101/gad.4.8.1365. [DOI] [PubMed] [Google Scholar]
  39. Sakaguchi M., Zenzie-Gregory B., Groopman J. E., Smale S. T., Kim S. Y. Alternative pathway for induction of human immunodeficiency virus gene expression: involvement of the general transcription machinery. J Virol. 1991 Oct;65(10):5448–5456. doi: 10.1128/jvi.65.10.5448-5456.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schöler H. R., Ciesiolka T., Gruss P. A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells. Cell. 1991 Jul 26;66(2):291–304. doi: 10.1016/0092-8674(91)90619-a. [DOI] [PubMed] [Google Scholar]
  41. Selby M. J., Bain E. S., Luciw P. A., Peterlin B. M. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 1989 Apr;3(4):547–558. doi: 10.1101/gad.3.4.547. [DOI] [PubMed] [Google Scholar]
  42. SenGupta D. N., Berkhout B., Gatignol A., Zhou A. M., Silverman R. H. Direct evidence for translational regulation by leader RNA and Tat protein of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7492–7496. doi: 10.1073/pnas.87.19.7492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Southgate C. D., Green M. R. The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function. Genes Dev. 1991 Dec;5(12B):2496–2507. doi: 10.1101/gad.5.12b.2496. [DOI] [PubMed] [Google Scholar]
  44. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  45. Suzan M., Salaun D., Neuveut C., Spire B., Hirsch I., Le Bouteiller P., Querat G., Sire J. Induction of NF-KB during monocyte differentiation by HIV type 1 infection. J Immunol. 1991 Jan 1;146(1):377–383. [PubMed] [Google Scholar]
  46. Turpin J. A., Vargo M., Meltzer M. S. Enhanced HIV-1 replication in retinoid-treated monocytes. Retinoid effects mediated through mechanisms related to cell differentiation and to a direct transcriptional action on viral gene expression. J Immunol. 1992 Apr 15;148(8):2539–2546. [PubMed] [Google Scholar]
  47. Viglianti G. A., Mullins J. I. Functional comparison of transactivation by simian immunodeficiency virus from rhesus macaques and human immunodeficiency virus type 1. J Virol. 1988 Dec;62(12):4523–4532. doi: 10.1128/jvi.62.12.4523-4532.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Viglianti G. A., Rubinstein E. P., Graves K. L. Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques. J Virol. 1992 Aug;66(8):4824–4833. doi: 10.1128/jvi.66.8.4824-4833.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Viglianti G. A., Sharma P. L., Mullins J. I. Simian immunodeficiency virus displays complex patterns of RNA splicing. J Virol. 1990 Sep;64(9):4207–4216. doi: 10.1128/jvi.64.9.4207-4216.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Vlach J., Pitha P. M. Hexamethylene bisacetamide activates the human immunodeficiency virus type 1 provirus by an NF-kappa B-independent mechanism. J Gen Virol. 1993 Nov;74(Pt 11):2401–2408. doi: 10.1099/0022-1317-74-11-2401. [DOI] [PubMed] [Google Scholar]
  51. Ways D. K., Dodd R. C., Bennett T. E., Hooker J. L., Earp H. S. Effect of retinoic acid on phorbol ester-stimulated differentiation and protein kinase C-dependent phosphorylation in the U937 human monoblastoid cell. Cancer Res. 1988 Oct 15;48(20):5779–5787. [PubMed] [Google Scholar]
  52. Winandy S., Renjifo B., Li Y., Hopkins N. Nuclear factors that bind two regions important to transcriptional activity of the simian immunodeficiency virus long terminal repeat. J Virol. 1992 Sep;66(9):5216–5223. doi: 10.1128/jvi.66.9.5216-5223.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES