Human T cell lymphotropic virus type I Tax activates IL-15R alpha gene expression through an NF-kappa B site

J M Mariner1, V Lantz, T A Waldmann

  • 1Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. marinerj@mail.nih.gov

Insights

Human T cell lymphotropic virus type I (HTLV-I) infection elevates Interleukin-15 receptor alpha (IL-15Ralpha). The HTLV-I Tax protein upregulates IL-15Ralpha via NF-kappaB, suggesting a role in disease.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Interleukin-15 (IL-15) mRNA levels are elevated in diseases associated with human T cell lymphotropic virus type I (HTLV-I).
  • IL-15Ralpha is the specific binding receptor for IL-15.

Purpose of the Study:

  • To investigate the role of IL-15Ralpha in HTLV-I infection.
  • To elucidate the mechanism by which HTLV-I Tax protein influences IL-15Ralpha expression.

Main Methods:

  • Quantification of IL-15Ralpha mRNA and protein levels in HTLV-I-infected cells.
  • Analysis of IL-15Ralpha promoter activity using reporter constructs.
  • Investigation of the role of NF-kappaB in Tax-mediated IL-15Ralpha regulation through promoter deletion and gel shift assays.

Main Results:

  • IL-15Ralpha mRNA and protein levels were significantly increased in HTLV-I-infected cells.
  • Transient expression of HTLV-I Tax protein led to elevated IL-15Ralpha mRNA levels.
  • Tax expression increased IL-15Ralpha promoter activity by over 4-fold, mediated by NF-kappaB binding to a specific motif.

Conclusions:

  • IL-15Ralpha is transcriptionally regulated by the HTLV-I Tax protein.
  • The Tax protein activates IL-15Ralpha expression, in part, through the induction of NF-kappaB.
  • Upregulation of IL-15Ralpha may contribute to aberrant T cell proliferation in HTLV-I-associated diseases.

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