人类免疫缺陷病毒感染时大量释放 CD9+ 微囊泡，与病毒学控制无关。
Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control.
机构信息
Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur)-Complexo Hospitalario Universitario de Vigo, SERGAS-UVigo, Spain.
Section of Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
J Infect Dis. 2022 Mar 15;225(6):1040-1049. doi: 10.1093/infdis/jiaa375.
BACKGROUND
The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls.
METHODS
Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction.
RESULTS
Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients.
CONCLUSIONS
A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.
背景
细胞外囊泡（EVs）在人类免疫缺陷病毒（HIV）发病机制中的作用尚不清楚。我们研究了血浆微囊泡（MVs）的细胞起源，MVs 是一种胞吐衍生的 EV 类型，MV 中存在线粒体，以及它们与 HIV 感染患者和对照组中循环无细胞线粒体脱氧核糖核酸（ccf-mtDNA）的关系。
方法
定义了五个实验组：30 名未接受抗逆转录病毒治疗（ART）的患者；30 名接受 ART 治疗且病毒载量不可检测的患者；30 名精英控制者；30 名病毒载量控制者；30 名 HIV 未感染者。通过流式细胞术从血浆样本中定量和表征微囊泡。用 MitoTrackerDeepRed 鉴定含有线粒体的 MV，并用实时聚合酶链反应定量 ccf-mtDNA。
结果
与对照组相比，所有 HIV 感染组的微囊泡数量至少增加了 10 倍。超过 79%的微囊泡来源于血小板。与对照组相比，HIV 感染者中含有线粒体的 MV 比例（22.3%比 41.6%）和 MV 线粒体密度（706 比 1346）显著降低，在接受 ART 的患者中最低。微囊泡数量与 ccf-mtDNA 水平相关，HIV 感染者的 ccf-mtDNA 水平更高。
结论
在 HIV 感染期间，大量释放血小板衍生的 MV。一些 MV 含有线粒体，但与对照组相比，其比例和线粒体密度较低。血小板衍生的 MV 可能是血小板活化的标志物，即使在没有 HIV 复制的情况下，也可能反映发病机制。
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