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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

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Background

HTLV-1 and HTLV-2 trans-activating proteins (Tax1, Tax2) differ with respect to their ability to activate genes regulating viral replication, latency, and host cellular immune responses. Although HTLV-2 infections are usually asymptomatic, immunologic alterations are observed. We previously showed that HTLV-2 tax/rex viral load was upregulated in patients with HIV-1/HTLV-2 co-infection. This correlated with higher CD4+ T cell counts and improved health outcomes, possibly due to induction of CC-chemokines.

Methods

In this study, recombinant Tax1 and Tax2 proteins were expressed in E. coli. PBMCs were incubated with different concentrations of Tax proteins (10-100 pM). Supernatant fluids and cells were harvested at multiple time points for quantitative determinations of MIP-1alpha/CCL3, MIP-1beta/CCL4, RANTES/CCL5, and CCR5 receptor expression.

Results

In preliminary experiments it was shown that PMBCs from HTLV-2 infected donors had significantly lower levels of CCR5 expression and higher levels of RANTES/CCL5 compared to HTLV-2 seronegative donors (p<0.05). Tax1 and Tax2-treated PBMCs showed increased viability over a seven day period compared to controls (p<0.01). Both Tax1 and Tax2 induced equally high levels of all three CC-chemokines compared to mock-treated controls (p<0.05). Tax2-treated PBMCs showed a significantly lower percentage of CCR5-PE positive cells compared to mock-treated PBMCs within the gated lymphocyte population (p<0.05).

Conclusions

Recombinant Tax2 is a potent modulator of CC-chemokines and CCR5 in vitro. Further investigations are needed to determine the underlying mechanism(s), and whether Tax2 recapitulates the observed effects in vivo.

Author information

Correspondence to Christy S Barrios or Mark A Beilke.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Multiple Time Point
  • Human Peripheral Blood Mononuclear Cell
  • CCR5 Receptor
  • CCR5 Expression
  • Immunologic Alteration