TY - JOUR TI - Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members AU - Gonzalo-Gil, Elena AU - Rapuano, Patrick B AU - Ikediobi, Uchenna AU - Leibowitz, Rebecca AU - Mehta, Sameet AU - Coskun, Ayse K AU - Porterfield, J Zachary AU - Lampkin, Teagan D AU - Marconi, Vincent C AU - Rimland, David AU - Walker, Bruce D AU - Deeks, Steven AU - Sutton, Richard E A2 - Garrett, Wendy S A2 - Kirchhoff, Frank A2 - Kirchhoff, Frank A2 - Diaz-Griffero, Felipe VL - 8 PY - 2019 DA - 2019/04/09 SP - e44360 C1 - eLife 2019;8:e44360 DO - 10.7554/eLife.44360 UR - https://doi.org/10.7554/eLife.44360 AB - HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable. KW - HIV KW - ccr5 KW - transcription KW - elite controllers KW - viremic controllers KW - ccr2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -