Collazo Bryan Jael, Ortiz-Valentín Lorivette, Negrón-Rodríguez Cristhian G, Medina-Colón Juan Carlos, Cantres-Rosario Yisel M, Rodríguez Elaine, Wojna Valerie, Gerena Yamil
Department of Pharmacology and Toxicology, Medical Sciences Campus, University of Puerto Rico, San Juan, 00936-5067, Puerto Rico.
Department of Microbiology and Medical Zoology, Medical Sciences Campus, University of Puerto Rico, San Juan, 00936-5067, Puerto Rico.
J Neurovirol. 2025 Feb;31(1):95-107. doi: 10.1007/s13365-024-01240-9. Epub 2025 Jan 30.
The role of plasma exosomes from people living with HIV (PLWH) with HAND in the phenotypic profile of uninfected monocytes remains unknown. We hypothesized that these exosomes influence the CD14/CD16 phenotypical profile of uninfected monocytes in a time-dependent manner. Exosomes were collected via ultracentrifugation from the plasma of women living with HIV (WLWH) and healthy controls stratified according to their cognition into normal cognition (NC) or symptomatic neurocognitive impairment (SNI) groups. Monocyte subsets were identified via flow cytometry by using anti-CD14 and anti-CD16 fluorescent antibodies. Exosome uptake and changes in the percentages of monocyte subpopulations were analyzed from 1 to 24 h. The following results were obtained. (1) The uptake of HIV-negative exosomes by total uninfected monocytes was observed at 24 h, whereas the uptake of HIV-positive exosomes was observed at an earlier time point at 6 h. (2) HIV-positive exosomes significantly decreased the percentage of classical monocytes and increased intermediate and nonclassical monocytes at 24 h. (3) The uptake of NC exosomes was observed at an early time point at 6 h compared with SNI in all of the monocyte subsets. (4) Higher percentages of monocyte subsets were observed when cells were exposed to NC exosomes at 1 h, 6 h, or 24 h than when monocytes were exposed to exosomes from SNI patients. Our findings may help to identify new targets and molecular mechanisms that are involved in the pathogenesis of HAND.
感染人类免疫缺陷病毒(HIV)且患有与HIV相关的神经认知障碍(HAND)的人群血浆外泌体在未感染单核细胞表型特征中的作用尚不清楚。我们推测这些外泌体会以时间依赖的方式影响未感染单核细胞的CD14/CD16表型特征。通过超速离心从感染HIV的女性(WLWH)血浆中收集外泌体,并根据认知情况将健康对照分为正常认知(NC)或有症状神经认知障碍(SNI)组。使用抗CD14和抗CD16荧光抗体通过流式细胞术鉴定单核细胞亚群。在1至24小时内分析外泌体摄取情况以及单核细胞亚群百分比的变化。获得了以下结果。(1)在24小时观察到未感染的总单核细胞对HIV阴性外泌体的摄取,而在较早的6小时时间点观察到对HIV阳性外泌体的摄取。(2)在24小时时,HIV阳性外泌体显著降低了经典单核细胞的百分比,并增加了中间型和非经典单核细胞的百分比。(3)与SNI相比,在所有单核细胞亚群中,在6小时这个较早的时间点观察到了对NC外泌体的摄取。(4)当细胞在1小时、6小时或24小时暴露于NC外泌体时,观察到的单核细胞亚群百分比高于单核细胞暴露于SNI患者外泌体时的百分比。我们的研究结果可能有助于确定HAND发病机制中涉及的新靶点和分子机制。