HIV latency and integration site placement in five cell-based models.
HIV latency and integration site placement in five cell-based models.
复制标题
DOI：
10.1186/1742-4690-10-90
复制
发表时间：
2013-08-16
期刊：
影响因子：
3.3
通讯作者：
Bushman FD
中科院分区：
文献类型：
--
作者：
Sherrill-Mix S;Lewinski MK;Famiglietti M;Bosque A;Malani N;Ocwieja KE;Berry CC;Looney D;Shan L;Agosto LM;Pace MJ;Siliciano RF;O'Doherty U;Guatelli J;Planelles V;Bushman FD
HIV感染可以用抗逆转录病毒药物有效治疗，但是潜伏的整合前病毒库的持续存在阻止了从感染个体中根除HIV。整合前病毒的染色体环境已被提出影响HIV潜伏期，但转录抑制的决定因素尚未完全阐明，目前还不清楚是否相同的分子机制驱动不同细胞培养模型中的潜伏期。在这里，我们比较了基于原代人T细胞或T细胞系的五种不同体外潜伏期模型的数据。在体外感染细胞，并将其分离成含有表达或沉默/诱导型前病毒的级分，并对每个级分的整合位点群体进行测序。我们比较了6，252个表达的前病毒与6，184个沉默/诱导型前病毒的位置，涉及140种形式的基因组注释，其中许多是在多种长度的染色体间隔上分析的。将前病毒表达状态与基因组特征联系起来的正则化逻辑回归模型显示，没有比机会表现更好的潜伏期预测因子，尽管几个基因组特征与个体模型中的前病毒表达显著相关。如果它们来自相同的细胞培养模型，则相同染色体区域中的前病毒确实倾向于共享相同的表达或沉默/诱导状态，但如果它们来自不同的模型，则不是。沉默/诱导表型似乎与染色体位置相关，但分子基础尚未完全阐明，并且在体外潜伏模型中可能有所不同。
HIV infection can be treated effectively with antiretroviral agents, but the persistence of a latent reservoir of integrated proviruses prevents eradication of HIV from infected individuals. The chromosomal environment of integrated proviruses has been proposed to influence HIV latency, but the determinants of transcriptional repression have not been fully clarified, and it is unclear whether the same molecular mechanisms drive latency in different cell culture models. Here we compare data from five different in vitro models of latency based on primary human T cells or a T cell line. Cells were infected in vitro and separated into fractions containing proviruses that were either expressed or silent/inducible, and integration site populations sequenced from each. We compared the locations of 6,252 expressed proviruses to those of 6,184 silent/inducible proviruses with respect to 140 forms of genomic annotation, many analyzed over chromosomal intervals of multiple lengths. A regularized logistic regression model linking proviral expression status to genomic features revealed no predictors of latency that performed better than chance, though several genomic features were significantly associated with proviral expression in individual models. Proviruses in the same chromosomal region did tend to share the same expressed or silent/inducible status if they were from the same cell culture model, but not if they were from different models. The silent/inducible phenotype appears to be associated with chromosomal position, but the molecular basis is not fully clarified and may differ among in vitro models of latency.
登录
查看更多内容
影响因子：
1.7
作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
通讯作者：
Walichiewicz, J
影响因子：
6.4
作者：
Chang ST;Sova P;Peng X;Weiss J;Law GL;Palermo RE;Katze MG
通讯作者：
Katze MG
影响因子：
5.4
作者：
Coull, JJ;Romerio, F;Margolis, DM
通讯作者：
Margolis, DM
影响因子：
20.3
作者：
Bosque, Alberto;Planelles, Vicente
通讯作者：
Planelles, Vicente
影响因子：
4.8
作者：
Bosque, Alberto;Planelles, Vicente
通讯作者：
Planelles, Vicente