title: 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.
abstract: 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.
authors.affiliation: Infectious Diseases Division, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Research Service 151-I, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Barrios
authors.forename: L
authors.initials: L
authors.lastname: Castillo
authors.forename: H
authors.initials: H
authors.lastname: Zhi
authors.forename: C-Z
authors.initials: CZ
authors.lastname: Giam
authors.forename: M A
authors.initials: MA
authors.lastname: Beilke
mesh_terms: D002460:Cell Line; D019742:Chemokines, CC / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016356:Gene Products, tax / Q000276:immunology*; D015491:HTLV-II Infections / Q000276:immunology* / Q000473:pathology; D015367:Human T-lymphotropic virus 2 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D051996:Transcription Factor RelA / Q000276:immunology*
chemical_list: D019742:Chemokines, CC; D016356:Gene Products, tax; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; C514971:tax protein, Human T-lymphotrophic virus 2
keywords: CC-chemokines; HTLV-2; NF-κB pathway; Tax2; innate immunity