Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses.
Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses.
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单个HIV-1前病毒的转录、整合和序列的平行分析。
DOI：
10.1016/j.cell.2021.12.011
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发表时间：
2022-01-20
期刊：
影响因子：
64.5
通讯作者：
Lichterfeld M
中科院分区：
文献类型：
--
作者：
Einkauf KB;Osborn MR;Gao C;Sun W;Sun X;Lian X;Parsons EM;Gladkov GT;Seiger KW;Blackmer JE;Jiang C;Yukl SA;Rosenberg ES;Yu XG;Lichterfeld M
尽管抗逆转录病毒治疗（ART）仍然存在的HIV-1感染细胞通常被认为是“转录沉默”，但在某些细胞中可能会发生活跃的病毒基因表达，这对病毒潜伏期的概念提出了挑战。应用分析转录活性和单个前病毒的染色体位置的测定，我们描述了转录活性和沉默前病毒物种的全球基因组和表观遗传图谱，并评估了它们在接受抑制性ART的人中的纵向进化。我们发现前病毒的转录活性与激活整合位点线性邻近的表观遗传染色质特征相关，染色体间和染色体内接触区。在延长的ART期间，转录活性前病毒被积极选择;然而，这种模式被病毒感染细胞的大克隆所破坏，这些细胞可能通过升高的内在增殖活性而胜过负选择力。我们的研究结果表明，转录活性的前病毒是动态演变的选择压力下，由主机因素。介绍了一种用于HIV-1储库细胞分析的多维检测方法（PRIP-seq）在ART期间主动选择具有转录活性的HIV-1前病毒大的转录活性前病毒克隆抵抗阴性宿主选择力线性和3D染色质接触中的表观遗传信号影响HIV-1转录PRIP-seq是一种多维单细胞测定，其同时捕获前病毒序列，相应的染色体整合位点，以及HIV-1 RNA在单个病毒感染细胞中的表达，并允许在接受抑制性抗逆转录病毒治疗的患者中对转录活性和沉默前病毒进行全局定位。
HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered “transcriptionally silent,” but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors. A multidimensional assay for HIV-1 reservoir cell profiling is presented (PRIP-seq) Transcriptionally active HIV-1 proviruses are actively selected against during ART Large transcriptionally active proviral clones resist negative host selection forces Epigenetic signals in linear and 3D chromatin contacts influence HIV-1 transcription PRIP-seq is a multidimensional single-cell assay that simultaneously captures the proviral sequence, the corresponding chromosomal integration site, and the expression of HIV-1 RNA in single virally infected cells and allows for the global mapping of transcriptionally active and silent proviruses in patients receiving suppressive antiretroviral therapy.
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影响因子：
6
作者：
Crowley C;Yang Y;Qiu Y;Hu B;Abnousi A;Lipiński J;Plewczyński D;Wu D;Won H;Ren B;Hu M;Li Y
通讯作者：
Li Y
影响因子：
16.6
作者：
Cesana D;Santoni de Sio FR;Rudilosso L;Gallina P;Calabria A;Beretta S;Merelli I;Bruzzesi E;Passerini L;Nozza S;Vicenzi E;Poli G;Gregori S;Tambussi G;Montini E
通讯作者：
Montini E
影响因子：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
64.8
作者：
Chun, TW;Carruth, L;Siliciano, RF
通讯作者：
Siliciano, RF
影响因子：
4.6
作者：
Amemiya, Haley M.;Kundaje, Anshul;Boyle, Alan P.
通讯作者：
Boyle, Alan P.