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Distinct transcriptomic profiles of naïve CD4+ T cells distinguish HIV-1 infected patients initiating antiretroviral therapy at acute or chronic phase of infection
Genomics ( IF 4.4 ) Pub Date : 2021-08-20 , DOI: 10.1016/j.ygeno.2021.08.014
Stefan Petkov 1 , Francesca Chiodi 1
Affiliation  

We analyzed the whole transcriptome characteristics of blood CD4+ T naïve (TN) cells isolated from HIV-1 infected patients starting ART at acute (early ART = EA; n = 13) or chronic (late ART = LA; n = 11) phase of infection and controls (C; n = 15). RNA sequencing revealed 389 differentially expressed genes (DEGs) in EA and 810 in LA group in relation to controls. Comparison of the two groups of patients showed 183 DEGs. We focused on DEGs involved in apoptosis, inflammation and immune response. Clustering showed a poor separation of EA from C suggesting that these two groups present a similar transcriptomic profile of CD4+ TN cells. The comparison of EA and LA patients resulted in a high cluster purity revealing that different biological dysfunctions characterize EA and LA patients. The upregulated expression of several inflammatory chemokine genes distinguished the patient groups from C; CCL2 and CCL7, however, were downregulated in EA compared to LA patients. BCL2, an anti-apoptotic factor pivotal for naïve T cell homeostasis, distinguished both EA and LA from C. The expression of several DEGs involved in different inflammatory processes (TLR4, PTGS2, RAG1, IFNA16) was lower in EA compared LA. We conclude that although the transcriptome of CD4+ TN cells isolated from patients initiating ART at acute infection reveals a more quiescent phenotype, the survival profile of these cells still appears to be affected. Our results show that the detrimental process of inflammation is under more efficient control in EA patients.



中文翻译:

初始 CD4+ T 细胞的不同转录组学特征区分 HIV-1 感染患者在急性或慢性感染阶段开始抗逆转录病毒治疗

我们分析了从急性(早期 ART = EA; n  = 13)或慢性(晚期 ART = LA;n  = 11)开始 ART 的 HIV-1 感染患者分离的血液 CD4+ T naïve (TN) 细胞的全转录组特征感染和控制(C;n  = 15)。RNA 测序显示 EA 中的 389 个差异表达基因 (DEG) 和 LA 组中的 810 个与对照相关。两组患者比较显示183°。我们专注于参与细胞凋亡、炎症和免疫反应的 DEG。聚类显示 EA 与 C 的分离较差,表明这两组呈现出相似的 CD4+ T N转录组学特征细胞。EA 和 LA 患者的比较导致高簇纯度,表明不同的生物功能障碍是 EA 和 LA 患者的特征。几种炎症趋化因子基因的上调表达将患者组与 C 区区分开来;然而,与 LA 患者相比,CCL2 和 CCL7 在 EA 中下调。BCL2 是一种对幼稚 T 细胞稳态至关重要的抗凋亡因子,将 EA 和 LA 与 C 区分开来。与 LA 相比,EA 中参与不同炎症过程的几种 DEG(TLR4、PTGS2、RAG1、IFNA16)的表达较低。我们得出结论,虽然 CD4+ T N的转录组从在急性感染时开始 ART 的患者中分离的细胞显示出更静止的表型,这些细胞的存活率似乎仍然受到影响。我们的结果表明,炎症的有害过程在 EA 患者中得到更有效的控制。

更新日期:2021-08-25
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