Agudelo Juan Sebastian Henao, Pereira Gabriel, Fernandes Célio Junior da Costa
Faculty of Health Sciences, Central Unit of Valle del Cauca (UCEVA), Tulua 763022, Valle del Cauca, Colombia.
School of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo 04021-001, Brazil.
Viruses. 2025 May 31;17(6):807. doi: 10.3390/v17060807.
Severe dengue is a global health threat, affecting 4 billion people, with nearly 1 million hospitalizations during epidemics and around 25,000 annual deaths. Severe dengue presentations are characterized by vascular leakage, hemorrhagic manifestations, and shock, which can lead to multiorgan failure. Recent studies highlight the crucial role of extracellular vesicles (EVs) in the pathogenesis of dengue, influencing immune response and disease progression. EVs, nanometric structures secreted by cells, mediate viral dissemination, immune modulation, and endothelial dysfunction by transporting biomolecules such as microRNAs (miRNAs) and viral proteins. Infected cell-derived EVs carry viral components, including NS protein and miRNAs like miR-21 and miR-126-5p, which compromise endothelial integrity and activate immune pathways such as Toll-like receptor, NF-κB, and JAK-STAT signaling. This, together with the immune response, leads to the release of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IFN-γ. EVs also facilitate viral immune evasion by suppressing antiviral responses. Recent analyses of miRNAs within EVs suggest their potential as biomarkers for disease progression. Differentially expressed miRNAs in circulating EVs correlate with severe outcomes, providing tools for risk stratification and therapeutic monitoring. Advanced techniques, such as nanoparticle tracking analysis and flow cytometry, allow precise EV characterization, supporting their integration into clinical applications.
重症登革热是一种全球健康威胁，影响着40亿人，疫情期间有近100万人住院治疗，每年约有2.5万人死亡。重症登革热的表现特征为血管渗漏、出血表现和休克，可导致多器官功能衰竭。最近的研究强调了细胞外囊泡（EVs）在登革热发病机制中的关键作用，影响免疫反应和疾病进展。EVs是细胞分泌的纳米级结构，通过运输诸如微小RNA（miRNAs）和病毒蛋白等生物分子来介导病毒传播、免疫调节和内皮功能障碍。受感染细胞衍生的EVs携带病毒成分，包括NS蛋白以及如miR-21和miR-126-5p等miRNAs，这些成分会损害内皮完整性并激活诸如Toll样受体、NF-κB和JAK-STAT信号传导等免疫途径。这与免疫反应一起，导致促炎细胞因子的释放，包括TNF-α、IL-1β、IL-6和IFN-γ。EVs还通过抑制抗病毒反应促进病毒免疫逃逸。最近对EVs内miRNAs的分析表明它们作为疾病进展生物标志物的潜力。循环EVs中差异表达的miRNAs与严重后果相关，为风险分层和治疗监测提供了工具。先进技术，如纳米颗粒跟踪分析和流式细胞术，可实现对EVs的精确表征，支持将其整合到临床应用中。
