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

Christy S. Barrios, Muna Abuerreish, Michael Dale Lairmore, Laura Castillo, Chou Zen Giam, Mark A. Beilke

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (10-100pM), 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 (100pM) 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.

Original languageEnglish (US)
Pages (from-to)429-439
Number of pages11
JournalViral Immunology
Volume24
Issue number6
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

tax Gene Products
Deltaretrovirus
Chemokines
CC Chemokines
Blood Cells
Down-Regulation
Human T-lymphotropic virus 2
Human T-lymphotropic virus 1
Lymphocytes
CCR Receptors
Cellular Microenvironment
Chemokine CCL5
Regulator Genes
Innate Immunity
Cellular Immunity
Proteins
Ligands
Gene Expression
Infection
Population

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Molecular Medicine

Cite this

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. / Barrios, Christy S.; Abuerreish, Muna; Lairmore, Michael Dale; Castillo, Laura; Giam, Chou Zen; Beilke, Mark A.

In: Viral Immunology, Vol. 24, No. 6, 01.12.2011, p. 429-439.

Research output: Contribution to journalArticle

@article{e29a07938a1d48eda235d211ee9dce15,
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 (10-100pM), 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 (100pM) 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.",
author = "Barrios, {Christy S.} and Muna Abuerreish and Lairmore, {Michael Dale} and Laura Castillo and Giam, {Chou Zen} and Beilke, {Mark A.}",
year = "2011",
month = "12",
day = "1",
doi = "10.1089/vim.2011.0037",
language = "English (US)",
volume = "24",
pages = "429--439",
journal = "Viral Immunology",
issn = "0882-8245",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - 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

AU - Barrios, Christy S.

AU - Abuerreish, Muna

AU - Lairmore, Michael Dale

AU - Castillo, Laura

AU - Giam, Chou Zen

AU - Beilke, Mark A.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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 (10-100pM), 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 (100pM) 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.

AB - 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 (10-100pM), 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 (100pM) 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.

UR - http://www.scopus.com/inward/record.url?scp=83255193383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83255193383&partnerID=8YFLogxK

U2 - 10.1089/vim.2011.0037

DO - 10.1089/vim.2011.0037

M3 - Article

VL - 24

SP - 429

EP - 439

JO - Viral Immunology

JF - Viral Immunology

SN - 0882-8245

IS - 6

ER -