Egaña-Gorroño Lander, Guardo Alberto C, Bargalló Manel E, Planet Evarist, Vilaplana Elisenda, Escribà Tuixent, Pérez Iñaki, Gatell Josep Maria, García Felipe, Arnedo Mireia, Plana M Montserrat
Group of Genomics and Pharmacogenomics of HIV, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
Immunopathology and Cellular Immunology, AIDS Research Group, Catalan project for the development of an HIV vaccine (HIVACAT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
PLoS One. 2016 May 12;11(5):e0155245. doi: 10.1371/journal.pone.0155245. eCollection 2016.
The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response.
miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms.
A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response.
Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response.
在HIV领域，宿主微小RNA（miRNA）、病毒控制和免疫反应之间的关系尚未阐明。本研究的目的是评估在病毒复制控制和免疫反应方面存在差异的HIV感染者的CD8 + T细胞中miRNA谱的差异。
使用Affymetrix miRNA 3.1芯片评估未感染个体（HIV阴性，n = 11）、精英控制者（EC，n = 15）、病毒血症控制者（VC，n = 15）、病毒血症进展者（VP，n = 13）以及接受治疗的HIV感染患者（ART，n = 14）静息和经CD3/CD28刺激的CD8 + T细胞中的miRNA谱。经过背景校正、分位数归一化和中位数平滑汇总后，将归一化数据拟合到线性模型。分析包括：组间静息样本；组间刺激样本；以及每组内刺激样本与静息样本的比较。使用生物信息学算法对推定的靶基因进行富集分析。
当将所有感染组的静息样本与HIV阴性样本进行比较时，观察到miRNA下调模式。当将EC、ART和HIV阴性组的刺激样本与VP组进行比较时，也观察到miRNA下调，其中hsa-miR-4492下调最为明显。尽管与各自的静息样本相比，刺激样本中观察到miRNA优先下调，但VP呈现出不同的miRNA表达模式。事实上，hsa-miR-155和hsa-miR-181a在VP中下调，而在其他组中，刺激后分别观察到上调或无差异。总体而言，功能富集分析表明，预测的靶基因参与信号转导途径、代谢调节、细胞凋亡和免疫反应。
静息CD8 + T细胞在HIV感染者之间未表现出miRNA表达差异，但与未感染个体不同。此外，VP的刺激CD8 + T细胞中存在特定的miRNA模式，这可能反映出CD8 + T细胞免疫反应方面的有害模式。
