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  • Meeting abstract
  • Open Access

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

  • 1Email author,
  • 1,
  • 1,
  • 2,
  • 3,
  • 4 and
  • 1
Retrovirology20118 (Suppl 1) :A98

https://doi.org/10.1186/1742-4690-8-S1-A98

  • Published:

Keywords

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

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.

Authors’ Affiliations

(1)
Division of Infectious Diseases, Medical College of Wisconsin and Research Service, Clement J Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53226, USA
(2)
Department of Veterinary Biosciences, Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
(3)
Departments of Laboratory Medicine and Epidemiology/Biostatistics, University of California, San Francisco, CA 94118, USA
(4)
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA

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