Data from: "Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts"

AbstractEliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.消除潜伏性HIV-1是艾滋病研究的核心目标之一，但决定这类病毒储存库规模的宿主调控因子仍未得到充分阐明。本研究探讨了在接受抑制性抗逆转录病毒治疗（antiretroviral therapy, ART）期间，宿主基因表达对HIV-1储存库规模的影响。我们对14名在急性感染期启动ART、且实现有效病毒抑制但总HIV-1 DNA水平存在差异的男性受试者的外周血细胞开展了单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）分析。差异表达分析结果显示，在HIV-1储存库无法被检出的受试者中，CD14+单核细胞的活性显著升高，且IL1B的表达水平与储存库规模呈负相关。这一发现于另一独立队列中得到验证，该队列包含38名不同血统、感染不同HIV-1亚型的男性受试者，并采用完整前病毒DNA检测（intact proviral DNA assay, IPDA®）进行相关指标测定。相互作用建模分析显示，当中枢记忆CD4+ T细胞（central memory CD4+ T cell）的频率较高时，单核细胞IL1B的表达与储存库规模呈负相关，这将单核细胞IL1B的表达与已知作为持续性HIV-1储存库的细胞类型建立了关联。功能实验分析表明，IL1B可激活核因子κB（nuclear factor kappa-B, NF-κB），在促进HIV-1有效感染的同时抑制病毒扩散，提示其具备天然的潜伏逆转活性，可用于清除接受ART治疗个体体内的病毒储存库。综上，本研究通过scRNA-seq分析揭示，在急性感染期启动ART的个体中，单核细胞IL1B的表达可降低HIV-1前病毒储存库的规模。