Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, United States.
Yale Center for Genome Analysis Bioinformatics group, Yale University School of Medicine, New Haven, United States.
Elife. 2019 Apr 9;8:e44360. doi: 10.7554/eLife.44360.
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 . 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 and 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 and , 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 / down-regulation, suggesting that the phenotype is heritable.
HIV +精英和病毒血症控制器（EC/VC）能够控制病毒感染，这也许是由于宿主遗传决定因素。我们鉴定出 16%（131 例中的 21 例）EC/VC 的 CD4+T 细胞具有针对 R5 嗜性 HIV 的耐药性，在引入. 后发生逆转。在巨噬细胞中未观察到 R5 耐药性，并且这种耐药性依赖于 T 细胞激活的方法。这些 EC/VC 的 CD4+T 细胞的 和 RNA 水平较低，CCR2 和 CCR5 细胞表面表达减少，以及分泌趋化因子的水平降低。尽管通过 ATAC-seq 具有更可及的染色质，但 T 细胞中的趋化因子受体 mRNA 半衰期没有变化，而是具有 和 转录的活性降低。其他附近的基因也下调，在染色体 3p21 上约 500 kb 的区域内。在一个指数 VC 的家族成员中也观察到了这种相同的 R5 耐药表型，也与 / 下调有关，这表明该表型是可遗传的。
