Abstract：
Dengue fever is a rapidly emerging tropical disease and an important cause of morbidity in its severe form worldwide. A wide spectrum of the pathophysiology is associated with the transition of dengue fever to severe dengue, which is driven by the host immune response and might reflect in patients\' proteome profile. This study aims to analyze the plasma from different phases of dengue-infected patients at two time points. A mass-spectrometry-based proteomic approach was utilized to understand the involvement of probable candidate proteins toward developing a more severe, hemorrhagic form of dengue fever. Dengue-infected hospital-admitted patients with <5 days of fever were included in this study. Patient samples from the acute phase were screened for the presence of NS1 antigen using ELISA and subjected to molecular serotyping. Dengue molecular serotype-confirmed patient samples, pairwise from acute and critical phases with healthy control were subjected to qualitative and quantitative proteomic analysis, and then pathway analysis was performed. The protein-protein interaction network between the dengue virus and host proteins was depicted in the search for proteins associated with severe dengue pathophysiology. An array of apolipoprotein, cytokines, and endothelial proteins in association with virus replication and endothelial dysfunction were validated as biomolecules involved in severe dengue pathophysiology.
摘要：
登革热是一种迅速出现的热带病，是世界范围内严重发病的重要原因。广泛的病理生理学与登革热向严重登革热的转变有关，这是由宿主免疫反应驱动的，可能反映在患者的蛋白质组谱中。本研究旨在分析登革热感染患者在两个时间点的不同阶段的血浆。基于质谱的蛋白质组学方法被用来了解可能的候选蛋白质对发展更严重，登革热的出血性形式。本研究包括发烧<5天的登革热感染的住院患者。使用ELISA筛选来自急性期的患者样品中NS1抗原的存在并进行分子血清分型。登革热分子血清型证实的患者样本，从急性和关键阶段与健康对照成对进行定性和定量蛋白质组学分析，然后进行途径分析。在寻找与严重登革热病理生理学相关的蛋白质时，描述了登革热病毒与宿主蛋白质之间的蛋白质-蛋白质相互作用网络。一系列载脂蛋白，细胞因子,与病毒复制和内皮功能障碍相关的内皮细胞蛋白被验证为涉及严重登革热病理生理的生物分子。
