美国MGH拉贡研究所Mathias Lichterfeld小组完成单个HIV-1前病毒转录、整合和序列的平行分析。相关论文于2022年1月12日在线发表在《细胞》杂志上。
研究人员应用一种方法来分析了单个前病毒的转录活性和染色体位置，描述了转录活跃和沉默的前病毒种类的全局基因组和表观遗传图谱，并评估了接受抑制性抗逆转录病毒疗法患者的纵向演化。利用全基因组的表观遗传学参考数据，结果表明，前病毒的转录活性与整合位点线性附近及其染色体间和染色体内接触区的激活表观遗传学特征有关。转录活跃的前病毒在长期的抗逆转录病毒疗法中被正向选择，然而，这种模式被大型的病毒感染细胞克隆所违反，这些细胞可能通过提高内在的增殖活性而超过了负向选择。这项结果表明，在宿主因素的选择压力下，转录活跃的前病毒正在动态地演化。
据悉，尽管有抗逆转录病毒疗法ART，但持续存在的HIV-1感染细胞经常被认为是"转录沉默的"，但活跃的病毒基因表达可能发生在一些细胞中，这对病毒潜伏期的概念是个挑战。
附：英文原文
Title: Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
Author: Kevin B. Einkauf, Matthew R. Osborn, Ce Gao, Weiwei Sun, Xiaoming Sun, Xiaodong Lian, Elizabeth M. Parsons, Gregory T. Gladkov, Kyra W. Seiger, Jane E. Blackmer, Chenyang Jiang, Steven A. Yukl, Eric S. Rosenberg, Xu G. Yu, Mathias Lichterfeld
Issue&Volume: 2022-01-12
Abstract: 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.
DOI: 10.1016/j.cell.2021.12.011
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01449-5