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

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.