Position effects influence HIV latency reversal

被引:133
作者
Chen, Heng-Chang [1 ,2 ]
Martinez, Javier P. [3 ]
Zorita, Eduard [1 ,2 ]
Meyerhans, Andreas [3 ,4 ]
Filion, Guillaume J. [1 ,2 ]
机构
[1] Barcelona Inst Sci & Technol, CRG, Genome Architecture Gene Regulat Stem Cells & Can, Barcelona, Spain
[2] Univ Pompeu Fabra, Barcelona, Spain
[3] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Infect Biol Grp, Barcelona, Spain
[4] ICREA, Barcelona, Spain
基金
欧洲研究理事会;
关键词
ACTIVE ANTIRETROVIRAL THERAPY; INTEGRATION SITE SELECTION; ACUTE INFECTION; IN-VITRO; TRANSCRIPTION; RESERVOIRS; BOUNDARIES; PARALLEL; GENES; VIVO;
D O I
10.1038/nsmb.3328
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:47 / 54
页数:8
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