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Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection.

Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection.
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Orlova-Fink N, Chowdhury FZ, Sun X, Harrington S, Rosenberg ES, Yu XG, Lichterfeld M,


Orlova-Fink N, Chowdhury FZ, Sun X, Harrington S, Rosenberg ES, Yu XG, Lichterfeld M, (click to view)

Orlova-Fink N, Chowdhury FZ, Sun X, Harrington S, Rosenberg ES, Yu XG, Lichterfeld M,

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AIDS (London, England) 31(16) 2211-2215 doi 10.1097/QAD.0000000000001630

Abstract
OBJECTIVE
The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1.

METHODS
CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences.

RESULTS
Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infected patients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells.

CONCLUSION
CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.

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