Perera Nilanka, Kumar Abhinav, Gangadharan Bevin, Ranasinghe Diyanath, Wijewickrama Ananda, Malavige Gathsaurie Neelika, Miller Joanna L, Zitzmann Nicole
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Department of Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda 10250, Sri Lanka.
Viruses. 2025 May 31;17(6):805. doi: 10.3390/v17060805.
Infections caused by dengue virus (DENV) result in significant morbidity and mortality. A proportion of infected individuals develop dengue haemorrhagic fever (DHF) characterized by circulatory collapse and multiorgan failure. Early detection of individuals likely to develop DHF could lead to improved outcomes for patients and help us use healthcare resources more efficiently. We identified proteins that are differentially regulated during early disease in peripheral blood mononuclear cells (PBMCs) of patients who subsequently developed DHF. Four dengue fever (DF), four DHF and two healthy control PBMCs were subjected to tandem mass tag mass spectrometry. Differentially regulated proteins were used to identify up- or down-regulated Gene Ontology pathways. One hundred and sixty proteins were differentially expressed in DENV-infected samples compared to healthy controls. PBMCs from DHF patients differentially expressed 90 proteins compared to DF; these were involved in down-regulation of platelet activation and aggregation, cell adhesion, and cytoskeleton arrangement pathways. Proteins involved in oxidative stress and p38 MAPK signalling were upregulated in DHF samples during early infection compared to DF. This study has identified 90 proteins differentially regulated in PBMCs that could potentially serve as biomarkers to identify patients at risk of developing DHF at an early disease stage.
登革病毒（DENV）引起的感染会导致严重的发病率和死亡率。一部分感染者会发展为登革出血热（DHF），其特征为循环衰竭和多器官功能衰竭。早期发现可能发展为DHF的个体，有助于改善患者的治疗效果，并帮助我们更有效地利用医疗资源。我们在随后发展为DHF的患者外周血单核细胞（PBMC）的早期疾病过程中，鉴定出了差异调节的蛋白质。对4例登革热（DF）患者、4例DHF患者和2例健康对照的PBMC进行了串联质谱标签质谱分析。利用差异调节的蛋白质来鉴定上调或下调的基因本体途径。与健康对照相比，160种蛋白质在DENV感染的样本中差异表达。与DF患者相比，DHF患者的PBMC有90种蛋白质差异表达；这些蛋白质参与血小板活化和聚集、细胞粘附及细胞骨架排列途径的下调。与DF相比，在早期感染期间，DHF样本中参与氧化应激和p38丝裂原活化蛋白激酶信号传导的蛋白质上调。本研究鉴定出了PBMC中90种差异调节的蛋白质，这些蛋白质有可能作为生物标志物，在疾病早期阶段识别有发展为DHF风险的患者。
