Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1993 Feb;67(2):1094–1099. doi: 10.1128/jvi.67.2.1094-1099.1993

Role of tumor necrosis factor alpha in activation and replication of the tat-defective human immunodeficiency virus type 1.

W Popik 1, P M Pitha 1
PMCID: PMC237467  PMID: 8419639

Abstract

Transcription of human immunodeficiency virus type 1 (HIV-1) depends on the function of the virus-encoded regulatory protein Tat, which interacts with the specific Tat response (TAR) element present in the leader sequence of all HIV-1 RNAs. In this study, we examined whether tumor necrosis factor alpha (TNF-alpha) can replace the requirement for a functional Tat protein. We found that TNF-alpha can induce expression of a latent, tat-defective virus and support its replication both in T cells and in primary mononuclear cells. Analysis of the transcriptional rate of the tat-defective HIV-1 transcriptional unit indicates that TNF-alpha stimulates the initiation of transcription but, in contrast to Tat protein, does not significantly reduce transcriptional polarity. Interestingly, we found that the processing of viral precursor proteins is altered in the absence of Tat. We propose that TNF-alpha-mediated induction of HIV-1 plays an essential role in the early stages of the virus life cycle and in viral latency.

Full text

PDF
1094

Images in this article

1095Image
on p.1095
1095Image
on p.1095
1096Image
on p.1096

Selected References

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

  1. 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]
  2. D'Addario M., Roulston A., Wainberg M. A., Hiscott J. Coordinate enhancement of cytokine gene expression in human immunodeficiency virus type 1-infected promonocytic cells. J Virol. 1990 Dec;64(12):6080–6089. doi: 10.1128/jvi.64.12.6080-6089.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. D'Addario M., Wainberg M. A., Hiscott J. Activation of cytokine genes in HIV-1 infected myelomonoblastic cells by phorbol ester and tumor necrosis factor. J Immunol. 1992 Feb 15;148(4):1222–1229. [PubMed] [Google Scholar]
  4. 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]
  5. Feinberg M. B., Baltimore D., Frankel A. D. The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc Natl Acad Sci U S A. 1991 May 1;88(9):4045–4049. doi: 10.1073/pnas.88.9.4045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fenyö E. M., Morfeldt-Månson L., Chiodi F., Lind B., von Gegerfelt A., Albert J., Olausson E., Asjö B. Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. J Virol. 1988 Nov;62(11):4414–4419. doi: 10.1128/jvi.62.11.4414-4419.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Garcia J. A., Harrich D., Soultanakis E., Wu F., Mitsuyasu R., Gaynor R. B. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation. EMBO J. 1989 Mar;8(3):765–778. doi: 10.1002/j.1460-2075.1989.tb03437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gimble J. M., Duh E., Ostrove J. M., Gendelman H. E., Max E. E., Rabson A. B. Activation of the human immunodeficiency virus long terminal repeat by herpes simplex virus type 1 is associated with induction of a nuclear factor that binds to the NF-kappa B/core enhancer sequence. J Virol. 1988 Nov;62(11):4104–4112. doi: 10.1128/jvi.62.11.4104-4112.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hsu M. C., Schutt A. D., Holly M., Slice L. W., Sherman M. I., Richman D. D., Potash M. J., Volsky D. J. Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist. Science. 1991 Dec 20;254(5039):1799–1802. doi: 10.1126/science.1763331. [DOI] [PubMed] [Google Scholar]
  12. Israël N., Hazan U., Alcami J., Munier A., Arenzana-Seisdedos F., Bachelerie F., Israël A., Virelizier J. L. Tumor necrosis factor stimulates transcription of HIV-1 in human T lymphocytes, independently and synergistically with mitogens. J Immunol. 1989 Dec 15;143(12):3956–3960. [PubMed] [Google Scholar]
  13. Jeang K. T., Shank P. R., Kumar A. Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8291–8295. doi: 10.1073/pnas.85.21.8291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kato H., Sumimoto H., Pognonec P., Chen C. H., Rosen C. A., Roeder R. G. HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992 Apr;6(4):655–666. doi: 10.1101/gad.6.4.655. [DOI] [PubMed] [Google Scholar]
  17. Kessler M., Mathews M. B. Premature termination and processing of human immunodeficiency virus type 1-promoted transcripts. J Virol. 1992 Jul;66(7):4488–4496. doi: 10.1128/jvi.66.7.4488-4496.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laspia M. F., Rice A. P., Mathews M. B. HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell. 1989 Oct 20;59(2):283–292. doi: 10.1016/0092-8674(89)90290-0. [DOI] [PubMed] [Google Scholar]
  19. Laspia M. F., Rice A. P., Mathews M. B. Synergy between HIV-1 Tat and adenovirus E1A is principally due to stabilization of transcriptional elongation. Genes Dev. 1990 Dec;4(12B):2397–2408. doi: 10.1101/gad.4.12b.2397. [DOI] [PubMed] [Google Scholar]
  20. Liu A. Y., Miskovsky E. P., Stanhope P. E., Siliciano R. F. Production of transmembrane and secreted forms of tumor necrosis factor (TNF)-alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones. Evidence for a TNF-alpha-independent cytolytic mechanism. J Immunol. 1992 Jun 15;148(12):3789–3798. [PubMed] [Google Scholar]
  21. Liu J., Perkins N. D., Schmid R. M., Nabel G. J. Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription. J Virol. 1992 Jun;66(6):3883–3887. doi: 10.1128/jvi.66.6.3883-3887.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lähdevirta J., Maury C. P., Teppo A. M., Repo H. Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Sep;85(3):289–291. doi: 10.1016/0002-9343(88)90576-1. [DOI] [PubMed] [Google Scholar]
  23. Marciniak R. A., Calnan B. J., Frankel A. D., Sharp P. A. HIV-1 Tat protein trans-activates transcription in vitro. Cell. 1990 Nov 16;63(4):791–802. doi: 10.1016/0092-8674(90)90145-5. [DOI] [PubMed] [Google Scholar]
  24. Merrill J. E., Koyanagi Y., Chen I. S. Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol. 1989 Oct;63(10):4404–4408. doi: 10.1128/jvi.63.10.4404-4408.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  26. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Hayward G. S., Pitha P. M. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408–7412. doi: 10.1073/pnas.84.21.7408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Pitha P. M. Herpes simplex virus type-1 can reactivate transcription of latent human immunodeficiency virus. Nature. 1987 Jan 1;325(6099):67–70. doi: 10.1038/325067a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Nakajima K., Martínez-Maza O., Hirano T., Breen E. C., Nishanian P. G., Salazar-Gonzalez J. F., Fahey J. L., Kishimoto T. Induction of IL-6 (B cell stimulatory factor-2/IFN-beta 2) production by HIV. J Immunol. 1989 Jan 15;142(2):531–536. [PubMed] [Google Scholar]
  30. Popik W., Pitha P. M. Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9573–9577. doi: 10.1073/pnas.88.21.9573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Popik W., Pitha P. M. Transcriptional activation of the tat-defective human immunodeficiency virus type-1 provirus: effect of interferon. Virology. 1992 Aug;189(2):435–447. doi: 10.1016/0042-6822(92)90567-9. [DOI] [PubMed] [Google Scholar]
  32. Quinn T. C., Piot P., McCormick J. B., Feinsod F. M., Taelman H., Kapita B., Stevens W., Fauci A. S. Serologic and immunologic studies in patients with AIDS in North America and Africa. The potential role of infectious agents as cofactors in human immunodeficiency virus infection. JAMA. 1987 May 15;257(19):2617–2621. [PubMed] [Google Scholar]
  33. Quinnan G. V., Jr, Masur H., Rook A. H., Armstrong G., Frederick W. R., Epstein J., Manischewitz J. F., Macher A. M., Jackson L., Ames J. Herpesvirus infections in the acquired immune deficiency syndrome. JAMA. 1984 Jul 6;252(1):72–77. [PubMed] [Google Scholar]
  34. Raj N. B., Pitha P. M. Two levels of regulation of beta-interferon gene expression in human cells. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3923–3927. doi: 10.1073/pnas.80.13.3923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ross E. K., Buckler-White A. J., Rabson A. B., Englund G., Martin M. A. Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. J Virol. 1991 Aug;65(8):4350–4358. doi: 10.1128/jvi.65.8.4350-4358.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shibuya H., Irie K., Ninomiya-Tsuji J., Goebl M., Taniguchi T., Matsumoto K. New human gene encoding a positive modulator of HIV Tat-mediated transactivation. Nature. 1992 Jun 25;357(6380):700–702. doi: 10.1038/357700a0. [DOI] [PubMed] [Google Scholar]
  37. Shirazi Y., Pitha P. M. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. J Virol. 1992 Mar;66(3):1321–1328. doi: 10.1128/jvi.66.3.1321-1328.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sodroski J., Rosen C., Wong-Staal F., Salahuddin S. Z., Popovic M., Arya S., Gallo R. C., Haseltine W. A. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985 Jan 11;227(4683):171–173. doi: 10.1126/science.2981427. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Sullenger B. A., Gallardo H. F., Ungers G. E., Gilboa E. Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation. J Virol. 1991 Dec;65(12):6811–6816. doi: 10.1128/jvi.65.12.6811-6816.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vengris V. E., Stollar B. D., Pitha P. M. Interferon externalization by producing cell before induction of antiviral state. Virology. 1975 Jun;65(2):410–417. doi: 10.1016/0042-6822(75)90046-x. [DOI] [PubMed] [Google Scholar]
  42. Vlach J., Pitha P. M. Activation of human immunodeficiency virus type 1 provirus in T-cells and macrophages is associated with induction of inducer-specific NF-kappa B binding proteins. Virology. 1992 Mar;187(1):63–72. doi: 10.1016/0042-6822(92)90295-z. [DOI] [PubMed] [Google Scholar]
  43. Vlach J., Pitha P. M. Herpes simplex virus type 1-mediated induction of human immunodeficiency virus type 1 provirus correlates with binding of nuclear proteins to the NF-kappa B enhancer and leader sequence. J Virol. 1992 Jun;66(6):3616–3623. doi: 10.1128/jvi.66.6.3616-3623.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wright S. C., Jewett A., Mitsuyasu R., Bonavida B. Spontaneous cytotoxicity and tumor necrosis factor production by peripheral blood monocytes from AIDS patients. J Immunol. 1988 Jul 1;141(1):99–104. [PubMed] [Google Scholar]

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

RESOURCES