Human T cell leukaemia virus type 2 tax protein mediates CC-chemokine expression in peripheral blood mononuclear cells via the nuclear factor kappa B canonical pathway

Authors

  • C. S. Barrios,

    1. Infectious Diseases Division, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
    2. Research Service 151-I, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA
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  • L. Castillo,

    1. Infectious Diseases Division, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
    2. Research Service 151-I, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA
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  • H. Zhi,

    1. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
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  • C.-Z. Giam,

    1. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
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  • M. A. Beilke

    Corresponding author
    1. Infectious Diseases Division, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
    2. Research Service 151-I, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA
    • Correspondence: M. A. Beilke, Division of Infectious Diseases, Medical College of Wisconsin, 9200 West Wisconsin Avenue, 5th Floor, Clinical Cancer Center, Milwaukee, WI 53226, USA.

      E-mail: mbeilke@mcw.edu

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Summary

Retroviral co-infections with human immunodeficiency virus type-1 (HIV-1) and human T cell leukaemia virus type 1 (HTLV-1) or type 2 (HTLV-2) are prevalent in many areas worldwide. It has been observed that HIV-1/HTLV-2 co-infections are associated with slower rates of CD4+ T cell decline and delayed progression to AIDS. This immunological benefit has been linked to the ability of Tax2, the transcriptional activating protein of HTLV-2, to induce the expression of macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4 and regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5 and to down-regulate the expression of the CCR5 co-receptor in peripheral blood mononuclear cells (PBMCs). This study aimed to assess the role of Tax2-mediated activation of the nuclear factor kappa B (NF-κB) signalling pathway on the production of the anti-viral CC-chemokines MIP-1α, MIP-1β and RANTES. Recombinant Tax1 and Tax2 proteins, or proteins expressed via adenoviral vectors used to infect cells, were tested for their ability to activate the NF-κB pathway in cultured PBMCs in the presence or absence of NF-κB pathway inhibitors. Results showed a significant release of MIP-1α, MIP-1β and RANTES by PBMCs after the activation of p65/RelA and p50. The secretion of these CC-chemokines was significantly reduced (P < 0·05) by canonical NF-κB signalling inhibitors. In conclusion, Tax2 protein may promote innate anti-viral immune responses through the activation of the canonical NF-κB pathway.

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