tuberculosis specific cells and the deleterious consequences of CMV specific cell persistence in HIV infected subjects. Although Th1Th17 and Th1 cells produce similar CCL3 and CCL5 levels, a superior CCR5 expression on Th1Th17 cells ex vivo argue in favor of their increased ability to support R5 HIV entry. find more information However, the expression of CXCR4 was similar on Th1Th17 Inhibitors,Modulators,Libraries and Th1 cells despite the fact that permissiveness to X4 HIV strains is restricted to Th1Th17 cells, suggesting the possibility that additional post entry mechanisms likely regulate HIV replication in Th1 cells. Indeed, a very recent study demonstrated that HIV restriction Inhibitors,Modulators,Libraries in CMV specific cells is medi ated by post entry antiviral mechanisms linked to type I IFN responses and the selective expression of TRIM22 and TRIM5 restriction factors.

Thus, understanding molecular differences Inhibitors,Modulators,Libraries between Th1Th17 and Th1 cells may provide new insights into molecular mechanisms of HIV permissiveness vs. restriction in primary CD4 T cell subsets and reveal new therapeutic avenues. In this study we aimed to identify molecular mechanisms underlying differences in HIV permissiveness between HIV permissive Th1Th17 and HIV resistant Th1 cells. This study provides a unique genome wide characterization of differential gene expression in Th1Th17 vs. Th1 cells, reveals pathways and biological functions linked to HIV permissiveness, and identifies the PPAR activation path way as the Achilles heel for HIV permissiveness that may be therapeutically targeted to limit viral replication in primary CD4 T cells. Results Superior HIV permissiveness in Th1Th17 vs.

Th1 cells upon exposure to replication competent and single round viruses The increased expression of CCR5 on Th1Th17 vs. Th1 cells suggests a superior ability of Th1Th17 cells to support HIV entry. To distinguish between entry and post entry regulation Inhibitors,Modulators,Libraries mechanisms, HIV integration in Th1Th17 and Th1 cells was quantified Inhibitors,Modulators,Libraries upon exposure to replication competent R5 HIV strain or single round VSV G pseudotyped HIV that enters cells independently of the HIV receptor CD4 and coreceptors CCR5 and CXCR4. To this aim, highly pure matched Th1Th17 and Th1 subsets were sorted by flow cytometry from four different donors, stimulated via CD3CD28 for 3 days, and exposed to HIV. HIV DNA integration in Th1Th17 vs. Th1 cells was significantly higher when cells were exposed to NL4.

3BAL GFP, similar to our previous findings. Differences were marginally significant when cells were exposed to HIV VSVG GFP. Levels of GFP expression, an indicator of HIV transcription, others were slightly higher in Th1Th17 vs. Th1 cells, with donor to donor variations being observed. Because the stage of cells differentiation may be linked to HIV permissiveness, we investigated the central memory vs. effector memory phenotype in Th1Th17 and Th1 subsets, using previously described markers.