Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression.
Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression.
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DOI：
10.1097/qai.0000000000000756
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发表时间：
2015-11-01
期刊：
影响因子：
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通讯作者：
Gilbert C
中科院分区：
文献类型：
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作者：
Hubert A;Subra C;Jenabian MA;Tremblay Labrecque PF;Tremblay C;Laffont B;Provost P;Routy JP;Gilbert C
由于对一些因素的了解还不够，抗逆转录病毒治疗 (ART) 无法完全纠正 HIV-1 感染患者普遍免疫激活和炎症的升高。细胞外囊泡（EV），包括几种细胞类型释放的外泌体和微泡，可能会导致免疫激活和功能障碍。 EV 的大小、丰度和含量似乎根据感染阶段、疾病进展和 ART 的不同而不同。我们检查了 EV 的大小和血浆中外泌体的丰度是否与细胞和组织活化以及病毒产生相关。使用 AChE 测定对血浆中乙酰胆碱酯酶 (AChE+) 外泌体进行定量。使用动态光散射分析 EV 尺寸。分别通过蛋白质印迹和实时聚合酶链反应检测 EV 中存在的蛋白质和 microRNA。研究发现，未接受过 ART 治疗的患者血浆中的外泌体更为丰富。未接受 ART 的患者的 EV 大小大于 ART 抑制的患者、精英控制者或健康对照受试者。外泌体丰度和 EV 大小均与 CD4/CD8 T 细胞比率以及中性粒细胞、血小板和 CD4 T 细胞计数呈负相关，与 CD8 T 细胞计数呈正相关。 CD4 T 细胞最低值与外泌体丰度之间存在负相关，但 EV 大小则不存在负相关。在未接受 ART 的患者中，miR-155 和 miR-223 的水平与 EV 丰度和大小呈强烈负相关，而 miR-92 则不然。监测循环 EV 和 EV 传播的 microRNA 是可能的，并且可能为 HIV-1 发病机制、疾病进展和相关炎症状态以及 ART 的功效和旨在减少免疫激活的治疗提供新的见解。
Because of factors only partly understood, the generalized elevated immune activation and inflammation characterizing HIV-1–infected patients are corrected incompletely with antiretroviral therapy (ART). Extracellular vesicles (EVs) including exosomes and microvesicles released by several cell types may contribute to immune activation and dysfunction. EV size, abundance, and content appear to differ according to infection phase, disease progression, and ART. We examined whether the size of EVs and the abundance of exosomes in plasma are associated with cell and tissue activation as well as with viral production. Acetylcholinesterase-bearing (AChE+) exosomes in plasma were quantified using an AChE assay. EV size was analyzed using dynamic light scattering. Proteins and microRNAs present in EVs were detected by Western blot and real-time polymerase chain reaction, respectively. Exosomes were found more abundant in the plasma of ART-naive patients. EV size was larger in ART-naive than in ART-suppressed patients, elite controllers, or healthy control subjects. Both exosome abundance and EV sizes were inversely correlated with CD4/CD8 T-cell ratio and neutrophil, platelet, and CD4 T-cell counts and positively correlated with CD8 T-cell counts. A negative correlation was found between CD4 T-cell nadir and exosome abundance, but not EV size. Levels of miR-155 and miR-223 but not miR-92 were strongly correlated negatively with EV abundance and size in ART-naive patients. Monitoring of circulating EVs and EV-borne microRNA is possible and may provide new insight into HIV-1 pathogenesis, disease progression, and the associated inflammatory state, as well as the efficacy of ART and the treatments intended to reduce immune activation.