Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research.

中文翻译：

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整合和克隆扩增在 HIV 感染中的作用：长寿和繁荣

病毒 DNA 整合到宿主基因组中是复制周期和逆转录病毒（包括 HIV）发病机制的核心事件。尽管大多数感染 HIV 的细胞会在体内迅速消除，但 HIV 也会感染在联合抗逆转录病毒疗法 (cART) 期间持续存在的长寿细胞。具有复制能力的 HIV 前病毒的细胞形成一个水库，尽管有 cART，但这种水库是在没有 cART 的情况下根除或控制感染的努力的中心。这些慢性感染的长寿命细胞的持久性机制尚不确定，但最近的研究表明，HIV 原病毒的存在对受感染的细胞具有持久的影响。带有整合前病毒的细胞可能会持续多年，进行克隆扩增，并产生具有复制能力的 HIV。即使是基因组有缺陷的原病毒也可以产生 HIV RNA，并可能有助于持续的 HIV 发病机制。对 HIV 感染细胞的新分析表明，随着时间的推移，在 cART 上，HIV 感染细胞群的组成发生了变化，感染细胞长期存在，前病毒整合到与细胞生长调节相关的基因中。在一些情况下，强有力的证据表明特定基因中前病毒的存在可能决定持久性、增殖或两者兼而有之。这些数据提出了一个有趣的可能性，即在引入 cART 后，选择过程会丰富细胞，其中原病毒整合到与细胞生长调节相关的基因中。在 cART 期间感染 HIV 的细胞群的动态性质尚不清楚，但可能对 HIV 储存库的组成产生深远影响，对 HIV 根除和控制策略产生重要影响。因此，整合研究将有助于了解病毒的持久性并为根除和控制策略提供信息。在这里，我们回顾了 HIV 整合的过程，整合在 HIV 储存库的持久性、克隆扩展中所起的作用，并强调了当前的挑战和未来研究的悬而未决的问题。