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Transactivation of human immunodeficiency virus type 1 long terminal repeats by cell surface tumor necrosis factor

W Tadmori1, D Mondal, I Tadmori

  • 1Department of Molecular Oncology, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121.

Journal of Virology
|December 1, 1991
PubMed

Insights

Cell surface tumor necrosis factor alpha (csTNF-alpha) primarily regulates HIV-1 LTR activation. Secreted TNF-alpha does not correlate with HIV-1 LTR activation, suggesting a novel role for csTNF-alpha in AIDS.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Tumor necrosis factor alpha (TNF-alpha) exists in both secreted and cell surface (csTNF-alpha) forms.
  • Activated monocytic and T cells express TNF-alpha.
  • The role of different TNF-alpha forms in Human Immunodeficiency Virus type 1 (HIV-1) regulation is not fully understood.

Purpose of the Study:

  • To investigate the specific role of cell surface TNF-alpha (csTNF-alpha) in regulating HIV-1 Long Terminal Repeat (LTR) activation.
  • To determine if secreted TNF-alpha correlates with HIV-1 LTR activation.

Main Methods:

  • Utilized promonocytic U937 and Epstein-Barr virus-transformed B-cell line BH1.
  • Employed anti-TNF-alpha antibodies to assess suppression of HIV-1 LTR.
  • Investigated effects of phorbol 12-myristate 13-acetate on HIV-1 LTR expression.
  • Assessed impact of cyclosporin A and serine protease inhibitors on TNF-alpha secretion and HIV-1 LTR activation.

Main Results:

  • csTNF-alpha was found to predominantly regulate HIV-1 LTR activation in U937 and BH1 cell lines.
  • Anti-TNF-alpha antibody suppressed both constitutive and induced HIV-1 LTR expression, mediated by csTNF-alpha.
  • No correlation was observed between secreted TNF-alpha levels and HIV-1 LTR activation.
  • Inhibition of TNF-alpha secretion did not affect HIV-1 LTR activation.

Conclusions:

  • Cell surface TNF-alpha, not secreted TNF-alpha, plays a key regulatory role in HIV-1 LTR activation.
  • These findings suggest a novel biological function for csTNF-alpha in the immunopathogenesis of Acquired Immunodeficiency Syndrome (AIDS).

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