Immunology Section, Laboratorio InmunoBiología Molecular (LIBM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Area of Immune System Pathology, Madrid, Spain.
Front Immunol. 2022 Apr 22;13:878630. doi: 10.3389/fimmu.2022.878630. eCollection 2022.
Early antiretroviral treatment (ART) in vertically acquired HIV-1-infection is associated with a rapid viral suppression, small HIV-1 reservoir, reduced morbimortality and preserved immune functions. We investigated the miRNA profile from vertically acquired HIV-1-infected young adults based on ART initiation delay and its association with the immune system activation. Using a microRNA panel and multiparametric flow cytometry, miRNome profile obtained from peripheral blood mononuclear cells and its association with adaptive and innate immune components were studied on vertically HIV-1-infected young adults who started ART early (EARLY, 0-53 weeks after birth) and later (LATE, 120-300 weeks). miR-1248 and miR-155-5p, were significantly upregulated in EARLY group compared with LATE group, while miR-501-3p, miR-548d-5p, miR-18a-3p and miR-296-5p were significantly downregulated in EARLY treated group of patients. Strong correlations were obtained between miRNAs levels and soluble biochemical biomarkers and immunological parameters including CD4 T-cell count and maturation by CD69 expression on CD4 T-cells and activation by HLA-DR on CD16 NK cell subsets for miR-1248 and miR-155-5p. In this preliminary study, a distinct miRNA signature discriminates early treated HIV-1-infected young adults. The role of those miRNAs target genes in the modulation of HIV-1 replication and latency may reveal new host signaling pathways that could be manipulated in antiviral strategies. Correlations between miRNAs levels and inflammatory and immunological markers highlight those miRNAs as potential biomarkers for immune inflammation and activation in HIV-1-infected young adults who initiated a late ART.
早期抗逆转录病毒治疗(ART)在垂直获得性 HIV-1 感染中与快速病毒抑制、较小的 HIV-1 储存库、降低发病率和死亡率以及保留免疫功能有关。我们根据开始 ART 的延迟时间研究了垂直获得性 HIV-1 感染的年轻成年人的 miRNA 谱及其与免疫系统激活的关系。使用 microRNA 面板和多参数流式细胞术,研究了早期(出生后 0-53 周)和晚期(120-300 周)开始 ART 的垂直 HIV-1 感染年轻成年人外周血单个核细胞中获得的 miRNome 谱及其与适应性和固有免疫成分的关系。与 LATE 组相比,EARLY 组中的 miR-1248 和 miR-155-5p 显著上调,而 miR-501-3p、miR-548d-5p、miR-18a-3p 和 miR-296-5p 在 EARLY 治疗组中显著下调。miRNA 水平与可溶性生化生物标志物和免疫参数之间存在强烈相关性,包括 CD4 T 细胞计数和 CD4 T 细胞上 CD69 表达的成熟以及 CD16 NK 细胞亚群上 HLA-DR 的激活。在这项初步研究中,一个独特的 miRNA 特征可区分早期治疗的 HIV-1 感染年轻成年人。这些 miRNA 的靶基因在 HIV-1 复制和潜伏中的作用可能揭示了新的宿主信号通路,这些信号通路可以在抗病毒策略中进行操纵。miRNA 水平与炎症和免疫标志物之间的相关性突出了这些 miRNA 作为 HIV-1 感染年轻成年人免疫炎症和激活的潜在生物标志物的作用,这些患者晚期开始了 ART。