Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Amsterdam, Netherlands.
JCI Insight. 2021 Aug 23;6(16):e150794. doi: 10.1172/jci.insight.150794.
Historically, naive cells have been considered inconsequential to HIV persistence. Here, we compared the contributions of naive and memory cells to the reservoirs of individuals with a spectrum of reservoir sizes and variable immunological control. We performed proviral sequencing of approximately 6000 proviruses from cellular subsets of 5 elite controllers (ECs) off antiretroviral therapy (ART) and 5 chronic progressors (CPs) on ART. The levels of naive infection were barely detectable in ECs and approximately 300-fold lower compared with those in CPs. Moreover, the ratio of infected naive to memory cells was significantly lower in ECs. Overall, the naive infection level increased as reservoir size increased, such that naive cells were a major contributor to the intact reservoir of CPs, whose reservoirs were generally very diverse. In contrast, the reservoirs of ECs were dominated by proviral clones. Critically, the fraction of proviral clones increased with cell differentiation, with naive infection predicting reservoir diversity. Longitudinal sequencing revealed that the reservoir of ECs was less dynamic compared with that of CPs. Naive cells play a critical role in HIV persistence. Their infection level predicts reservoir size and diversity. Moreover, the diminishing diversity of the reservoir as cellular subsets mature suggests that naive T cells repopulate the memory compartment and that direct infection of naive T cells occurs in vivo.
从历史上看，幼稚细胞被认为对 HIV 持续存在没有影响。在这里，我们比较了幼稚细胞和记忆细胞对具有一系列储库大小和可变免疫控制个体储库的贡献。我们对 5 名精英控制者（ECs）在停止抗逆转录病毒治疗（ART）后和 5 名慢性进展者（CPs）在 ART 治疗期间的细胞亚群中的约 6000 个前病毒进行了前病毒测序。ECs 中几乎检测不到幼稚感染，而与 CPs 相比，幼稚感染水平大约低 300 倍。此外，ECs 中感染幼稚细胞与记忆细胞的比例明显较低。总的来说，幼稚感染水平随着储库大小的增加而增加，因此幼稚细胞是 CPs 完整储库的主要贡献者，其储库通常非常多样化。相比之下，ECs 的储库主要由前病毒克隆组成。关键的是，前病毒克隆的比例随着细胞分化而增加，幼稚感染预测储库多样性。纵向测序显示，ECs 的储库与 CPs 的储库相比动态性较小。幼稚细胞在 HIV 持续存在中起着关键作用。它们的感染水平预测储库大小和多样性。此外，随着细胞亚群的成熟，储库的多样性减少表明幼稚 T 细胞重新填充记忆区，并且体内直接感染幼稚 T 细胞。
