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TLR2 ligation enhances HIV-1 replication in activated CCR6+CD4+ T cells by increasing virus entry and establishing a more permissive environment to infection.

TLR2 ligation enhances HIV-1 replication in activated CCR6+CD4+ T cells by increasing virus entry and establishing a more permissive environment to infection.
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Bolduc JF, Ouellet M, Hany L, Tremblay MJ,


Bolduc JF, Ouellet M, Hany L, Tremblay MJ, (click to view)

Bolduc JF, Ouellet M, Hany L, Tremblay MJ,

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Journal of virology 2016 12 07() pii

Abstract

In this study, we investigated the effect of TLR2 ligation on the permissiveness of activated CD4(+) T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4(+) T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit to study the effect of TLR2 triggering on virus production at both population and single-cell levels. We report here that HIV-1 replication is augmented in CD3/CD28-costimulated CCR6(+)CD4(+) T cells upon engagement of the cell surface TLR2. Additional studies indicate that a higher virus entry and polymerization of the cortical actin are seen in this cell subset following TLR2 stimulation. A TLR2-mediated increase in the level of phosphorylated NF-κB p65 subunit was also detected in CD3/CD28-costimulated CCR6(+)CD4(+) T cells. We propose that, upon antigenic presentation, an engagement of TLR2 acts specifically on CCR6(+)CD4(+) T cells by promoting virus entry in an intracellular milieu more favourable for productive HIV-1 infection.

IMPORTANCE
Following primary infection, HIV-1 induces an immunological and structural disruption of the gut mucosa, leading to bacterial translocation and release of microbial components in the bloodstream. These pathogen-derived constituents include several agonists of Toll-like receptors that may affect gut-homing CD4(+) T cells, such as those expressing the chemokine receptor CCR6, which are highly permissive to HIV-1 infection. We demonstrate that TLR2 ligation in CD3/CD28-costimulated CCR6(+)CD4(+) T cells leads to an enhanced virus production. Our results highlight the potential impact of bacterial translocation on the overall permissiveness of CCR6(+)CD4(+) T cells to productive HIV-1 infection.

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