title: Recombinant human T-cell leukemia virus types 1 and 2 Tax proteins induce high levels of CC-chemokines and downregulate CCR5 in human peripheral blood mononuclear cells.
abstract: Human T-cell leukemia viruses types 1 (HTLV-1) and 2 (HTLV-2) produce key transcriptional regulatory gene products, known as Tax1 and Tax2, respectively. Tax1 and Tax2 transactivate multiple host genes involved in cellular immune responses within the cellular microenvironment, including induction of genes encoding expression of CC-chemokines. It is speculated that HTLV Tax proteins may act as immune modulators. In this study, recombinant Tax1 and Tax2 proteins were tested for their effects on the viability of cultured peripheral blood mononuclear cells (PBMCs), and their ability to induce expression of CC-chemokines and to downregulate the level of CCR5 expression in PBMCs. PBMCs obtained from uninfected donors were cultured in a range of Tax1 and Tax2 concentrations (10-100 pM), and supernatant fluids were harvested at multiple time points for quantitative determinations of MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5. Treatment of PBMCs with Tax1 and Tax2 proteins (100 pM) resulted in a significant increase in viability over a 7-d period compared to controls (p<0.01). Both Tax1 and Tax2 induced high levels of all three CC-chemokines over the dosing range compared to mock-treated controls (p<0.05). The gated population of lymphocytes treated with Tax2, as well as lymphocytes from HTLV-2-infected donors, showed a significantly lower percentage of CCR5-positive cells compared to those of uninfected donors and from mock-treated lymphocytes, respectively (p<0.05). These results suggest that Tax1 and Tax2 could promote innate immunity in the extracellular environment during HTLV-1 and HTLV-2 infections via CC-chemokine ligands and receptors.
authors: Infectious Diseases Division, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors: Christy S
authors: CS
authors: Barrios
authors: Muna
authors: M
authors: Abuerreish
authors: Michael D
authors: MD
authors: Lairmore
authors: Laura
authors: L
authors: Castillo
authors: Chou-Zen
authors: CZ
authors: Giam
authors: Mark A
authors: MA
authors: Beilke
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000276:immunology*; D003470:Culture Media / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D017930:Genes, Reporter; D015490:HTLV-I Infections / Q000276:immunology / Q000821:virology; D015491:HTLV-II Infections / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D015367:Human T-lymphotropic virus 2 / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: D019742:Chemokines, CC; D003470:Culture Media; D016356:Gene Products, tax; D019713:Receptors, CCR5; D011994:Recombinant Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; C514971:tax protein, Human T-lymphotrophic virus 2