1887

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection is frequently associated with concurrent infection by opportunistic pathogens, against which production of nitric oxide by host macrophages provides a first line of defence. We have investigated whether regulatory HIV-1 proteins, such as Tat, can modulate the activity of the inducible nitric oxide synthase () gene when expressed in stable transfectant lines of RAW264.7 cells. A bioassay for Tat, based on transactivation of an HIV-1 LTR-CAT reporter gene, allowed selection of Tat-expressing cells. Parental and Tat-expressing macrophages accumulated identical levels of nitrite following lipopolysaccharide (LPS) stimulation. Interferon γ (IFN-γ) stimulation however, resulted in reduced levels of nitrite accumulation as a direct consequence of Tat expression. Conditioned media from Tat-expressing cells reduced the level of nitrite accumulation in parental cells following IFN-γ stimulation but not stimulation with LPS. These results implicate HIV-1 Tat as a modulator of the IFN-γ-specific signal transduction pathways leading to expression.

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1996-08-01
2024-11-03
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References

  1. Biggs B. A., Hewish M., Kent S., Hayes K., Crowe S. M. 1995; HIV-1 infection of human macrophages impairs phagocytosis and killing of Toxoplasma gundii,. Journal of Immunology 154:6132–6139.
    [Google Scholar]
  2. Biswas D. K., Salas T. R., Wang C. M., Ahters B. J., Dezube B. J., Pardee A. B. 1995; A Tat-induced auto-up-regulatory loop for superactivation of the human immunodeficiency virus type-1 promoter. Journal of Virology 69:7437–7444
    [Google Scholar]
  3. Bukrinsky M. I., Nottet H. S. L. M., Schmidtmayerova H., Dubrovsky L., Flanagan C. R., Mullins M. E., Lipton S. A., Gendelman H. E. 1995; Regulation of nitric oxide synthase activity in human immunodeficiency type 1 (HlV-l)-infected monocytes: implications for HIV- associated neurological disease. Journal of Experimental Medicine 181:735–745
    [Google Scholar]
  4. Crowe S. M., Vardaxis N. J., Kent J., Maerz A. L., Hewish M. J., McGrath M. S., Mills J. 1994; HIV infection of monocyte-derived macrophages in vitro reduces phagocytosis of Candida albicans . Journal of Leukocyte Biology 56:318–327
    [Google Scholar]
  5. Crowle A. J., Ross E. R., Cohn D. L., Gilden J., May M. H. 1992; Comparison of the abilities of Mycobacterium avium and Mycobacterium intracellulare to infect and multiply in cultured human macrophages from normal and human immunodeficiency virus-infected subjects. Infection and Immunity 60:3697–3703
    [Google Scholar]
  6. Cullen B. R. 1991; Regulation of HIV-1 gene expression. FASEB journal 5:2361–2368
    [Google Scholar]
  7. Denis M., Ghadiran E. 1994; Alveolar macrophages from subjects infected with HIV-1 express macrophage inflammatory protein-la (MIP-1α): contribution to the CD8 + alveolitis. Clinical and Experimental Immunology 96:187–192
    [Google Scholar]
  8. Dingwall C. J., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A., Valerio R. 1989; Human immunodeficiency virus 1 Tat protein binds trans-activation responsive region (TAR) RNA in vitro. Proceedings of the National Academy of Sciences, USA 86:6925–6929
    [Google Scholar]
  9. Ensoli B., Buonaguro B. L., Barillari G., Fiorelli V., Gendelman R., Morgan R. A., Wingfield P., Gallo R. C. 1993; Release, uptake, and effects of extracellular human immunodeficiency virus type I Tat protein on cell growth and viral trans-activation. Journal of Virology 67:277–287
    [Google Scholar]
  10. Green S. J., Nacy C. A., Meltzer M. S. 1991; Cytokine-induced synthesis of nitrogen oxides in macrophages: a protective host response to Leishmania and other intracellular pathogens. Journal of Leukocyte Biology 50:93–103
    [Google Scholar]
  11. Hibbs J. B., Taintor R. R., Vavrin Z. 1987; Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235:473–476
    [Google Scholar]
  12. Iwamto G. K., Konicek S. A., Twigg H. L. 1994; Modulation of accessory cell-function and IL6 production by HIV-1 tat gene. American Journal of Respiratory Cell and Molecular Biology 10:580–585
    [Google Scholar]
  13. Jones K. A., Peterlin B. M. 1994; Control of RNA initiation and elongation at the HIV-1 promoter. Annual Review of Biochemistry 63:717–743
    [Google Scholar]
  14. Kent S. J., Stent G., Sonza S., Hunter S. D., Crowe S. M. 1994; HIV-1 infection of monocyte-derived macrophages reduces Fc and complement receptor expression. Clinical and Experimental Immunology 95:445–454
    [Google Scholar]
  15. Mosier D., Sieburg H. 1994; Macrophage-tropic HIV: critical for AIDS pathogenesis. Immunology Today 15:332–339
    [Google Scholar]
  16. Murphy K. M., Sweet M. J., Ross I. L., Hume D. A. 1993; Effects of tat and nef gene products of human immunodeficiency virus type 1 (HIV- 1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages. Journal of Virology 67:6954–6964
    [Google Scholar]
  17. Twigg H. L., Soliman D. A., Spain B. A. 1994; Impaired alveolar macrophage accessory cell function and reduced incidence of lymphocytic alveolitis in HIV-infected patients who smoke. AIDS 8:611–618
    [Google Scholar]
  18. Vodovotz V., Bogdan C., Paik J., Xie Q. -W., Nathan C. 1993; Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor. Journal of Experimental Medicine 178:605–613
    [Google Scholar]
  19. Xie Q. W., Whisnant R., Nathan C. 1993; Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide. Journal of Experimental Medicine 177:1779–1784
    [Google Scholar]
  20. Zauli G., Davis B. R., Re M. C., Visani G., Furlini G., la Placa M. 1992; Tat protein stimulates production of transforming growth factor-1 by marrow macrophages: a potential mechanism for human immunodeficiency virus-l-induced hematopoeitic suppression. Blood 80:3036–3043
    [Google Scholar]
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