Clinic of Infectious Diseases, Department of Medicine and Aging Sciences, University 'G. d'Annunzio' of Chieti-Pescara, Chieti.
Department of Medicine and Aging Sciences, University 'G. d'Annunzio' of Chieti-Pescara.
AIDS. 2021 Mar 15;35(4):595-604. doi: 10.1097/QAD.0000000000002794.
Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients.
We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a-/CD45-, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis.
Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients.
These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.
细胞外囊泡是通过细胞分裂释放的，由磷脂双层包围，携带蛋白质和遗传物质。已经表明，细胞外囊泡在几种情况下介导细胞间通讯，如炎症、免疫缺陷、肿瘤生长和病毒感染。在这里，我们分析了循环细胞外囊泡的水平，以阐明它们在表征 HIV 患者的慢性炎症机制中的作用。
我们通过最近开发的流式细胞术方法分析和分型循环细胞外囊泡。具体来说，鉴定并计数内皮衍生的细胞外囊泡（CD31+/CD41a-/CD45-，EMVs）、来自白细胞的细胞外囊泡（CD45+，LMVs）和血小板（CD41a+/CD31+）。此外，我们还通过蛋白质组学分析分析了细胞外囊泡的蛋白载量。
与健康受试者相比，HIV+患者的总细胞外囊泡、EMVs 和 LMVs 的循环水平显著降低，而血小板衍生的细胞外囊泡在患者中的水平高于健康人群。蛋白质组学分析显示，γIFN 和 IL1α 上调，而 OSM、NF-kB、LIF 和 RXRA 信号通路下调，表明这些患者的信号通路被激活。
这些数据首次表明，HIV 感染诱导产生含有可能促进慢性炎症和病毒复制的介质的细胞外囊泡。这两个效应是相互关联的，因为炎症本身会诱导病毒复制。因此，我们假设 HIV 感染抑制了携带抗炎分子的细胞外囊泡的产生。
