Position effects influence HIV latency reversal
Position effects influence HIV latency reversal
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DOI：
10.1038/nsmb.3328
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发表时间：
2017-01-01
影响因子：
16.8
通讯作者：
Filion, Guillaume J.
中科院分区：
文献类型：
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作者：
Chen, Heng-Chang;Martinez, Javier P.;Filion, Guillaume J.
治愈艾滋病毒的主要障碍是感染患者体内存在潜伏的原病毒。再激活疗法的部分成功表明，整合原病毒的基因组背景可能会干扰治疗。在这里，我们开发了一种称为 Barcoded HIV ensembles (B-HIVE) 的方法，用于绘制数千个单独原病毒的染色体位置，同时跟踪它们在受感染细胞群中的转录活动。 B-HIVE揭示，在Jurkat细胞中，HIV的表达在接近内源性增强子时最强。插入位点也会影响对潜伏期逆转剂的反应，因为我们发现植物血凝素和伏立诺他重新激活了插入在不同基因组位置的原病毒。根据这些结果，我们建议针对基因组所有区域的药物组合将是最有效的。总体而言，我们的数据表明，HIV 的插入环境是病毒对再激活疗法反应的关键决定因素。
The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers. The insertion site also affects the response to latency-reversing agents, because we found that phytohemagglutinin and vorinostat reactivated proviruses inserted at distinct genomic locations. From these results, we propose that combinations of drugs targeting all areas of the genome will be most effective. Overall, our data suggest that the insertion context of HIV is a critical determinant of the viral response to reactivation therapies.