Time course RNA-Seq of Innate Lymphoid Cells in Early Acute HIV Infection. Homo sapiens

We apply RNA-seq to limited populations of Innate Lymphoid Cells type 2 and type 3 (ILC2s and ILC3s, respectively) in human individuals infected with acute HIV in the FRESH study. We measured the whole transcriptome of ILC2s and ILC3s in both untreated (n=2) and ART treated (n=2) individuals over the course of infection, in order to compare these populations at key points during infection, namely: viral detection, peak viremia, and weeks past peak viremia (6-7 weeks post detection). Lacking true biological replicates, HIV- patients in the same study (n=9) were used as replicates to conduct Differential Expression (DE) analysis between time points in both ILC2s and ILC3s on a patient by patient basis. In untreated patients, ILC2s and ILC3s differentially expressed genes associated with apoptosis and cell death between peak viremia and viral detection, while ART treated patients' ILC2s and ILC3s demonstrated a mitigated response. Comparing 6-7 weeks after detection with peak viremia revealed a relative decrease in genes associated in cell death in untreated patients, while ART treated patients showed varied responses where several DE genes were associated with immune response. Overall design: RNA-seq of two Innate Lymphoid Cell populations in 2 HIV+ untreated patients, 2 HIV+ ART treated patients, and 9 HIV- patients (control, replicates).

本研究依托FRESH研究，对急性HIV感染人类受试者体内的有限量固有淋巴细胞2型和3型（Innate Lymphoid Cells type 2 and type 3，ILC2、ILC3）开展RNA测序（RNA-seq）。我们在整个感染进程中，分别检测了未接受治疗（n=2）与接受抗逆转录病毒治疗（Antiretroviral Therapy，ART，n=2）的受试者体内ILC2和ILC3的全转录组，以在感染关键时间节点——包括病毒检测阳性、病毒血症峰值以及病毒检测峰值后6-7周——对这两类细胞群进行比较分析。由于缺乏真实生物学重复（biological replicates），本研究中9名HIV阴性受试者被用作重复样本，以针对每名患者分别在ILC2和ILC3的各时间点之间开展差异表达（Differential Expression，DE）分析。在未接受治疗的患者中，ILC2与ILC3在病毒血症峰值与病毒检测阳性节点间存在与细胞凋亡（apoptosis）及细胞死亡相关的差异表达基因；而接受ART治疗的患者的ILC2和ILC3则表现出应答减弱的特征。将病毒检测峰值后6-7周与病毒血症峰值进行比较后发现，未接受治疗的患者体内与细胞死亡相关的基因表达量相对下降，而接受ART治疗的患者则呈现出多样化的应答，其中多个差异表达（DE）基因与免疫应答相关。总体实验设计：对2名未接受治疗的HIV阳性患者、2名接受ART治疗的HIV阳性患者以及9名HIV阴性患者（作为对照及生物学重复）的2种固有淋巴细胞群开展RNA测序。