Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Medicine and.
JCI Insight. 2018 Jul 12;3(13):99127. doi: 10.1172/jci.insight.99127.
The genomic integration of HIV into cells results in long-term persistence of virally infected cell populations. This integration event acts as a heritable mark that can be tracked to monitor infected cells that persist over time. Previous reports have documented clonal expansion in people and have linked them to proto-oncogenes; however, their significance or contribution to the latent reservoir has remained unclear. Here, we demonstrate that a directed pattern of clonal expansion occurs in vivo, specifically in gene pathways important for viral replication and persistence. These biological processes include cellular division, transcriptional regulation, RNA processing, and posttranslational modification pathways. This indicates preferential expansion when integration events occur within genes or biological pathways beneficial for HIV replication and persistence. Additionally, these expansions occur quickly during unsuppressed viral replication in vivo, reinforcing the importance of early intervention for individuals to limit reservoir seeding of clonally expanded HIV-infected cells.
HIV 基因组整合到细胞中会导致病毒感染细胞群体的长期持续存在。这种整合事件可作为一种可遗传的标记，用于追踪监测随时间推移而持续存在的受感染细胞。先前的报告已经记录了人群中的克隆扩增，并将其与原癌基因联系起来；然而，它们对潜伏储库的意义或贡献仍然不清楚。在这里，我们证明了一种在体内发生的定向克隆扩增模式，特别是在对病毒复制和持续存在至关重要的基因途径中。这些生物学过程包括细胞分裂、转录调控、RNA 处理和翻译后修饰途径。这表明当整合事件发生在有利于 HIV 复制和持续存在的基因或生物途径内时，会优先发生扩增。此外，这些扩增在体内未受抑制的病毒复制期间迅速发生，这强调了早期干预对于个体限制克隆扩增的 HIV 感染细胞储库播种的重要性。
