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差异蛋白质组学分析表明,新生感染基孔肯雅病毒的小鼠组织中的应激、炎症和凋亡途径与疾病发病机制有关。

Differential proteome analysis of Chikungunya virus-infected new-born mice tissues reveal implication of stress, inflammatory and apoptotic pathways in disease pathogenesis.

机构信息

Division of Virology, Defence Research and Development Establishment (DRDE), Gwalior, Madhya Pradesh, India.

出版信息

Proteomics. 2011 May;11(10):1936-51. doi: 10.1002/pmic.201000500. Epub 2011 Apr 7.

Abstract

Chikungunya infection is a major disease of public health concern. The recurrent outbreaks of this viral disease and its progressive evolution demands a potential strategy to understand major aspects of its pathogenesis. Unlike other alphaviruses, Chikungunya virus (CHIKV) pathogenesis is poorly understood. In every consecutive outbreak, some new symptoms associated with virulence and disease manifestations are being reported such as neurological implication, increased severity and enhanced vector competence. In order to unravel the mechanism of the disease process, proteomic analysis was performed to evaluate the host response in CHIKV-infected mice tissues. Comparative analysis of the multiple gels representing the particular tissue extract from mock and CHIKV-infected tissues revealed a drastic reprogramming of physiological conditions through 35 and 15 differentially expressed proteins belonging to different classes such as stress, inflammation, apoptosis, urea cycle, energy metabolism, etc. from liver and brain, respectively. Based on the alterations obtained in the CHIKV mouse model, most of the aspects of CHIKV infection such as disease severity, neurological complications, disease susceptibility and immunocompetence could be defined. This is the first report unravelling the complicated pathways involved in the mechanism of Chikungunya disease pathogenesis employing proteomic approach.

摘要

基孔肯雅热感染是一个主要的公共卫生关注疾病。这种病毒性疾病的反复爆发及其逐渐演变,需要一种潜在的策略来了解其发病机制的主要方面。与其他甲病毒不同,基孔肯雅病毒(CHIKV)的发病机制尚未得到充分理解。在每一次连续爆发中,都有一些与毒力和疾病表现相关的新症状被报道,如神经影响、严重程度增加和增强的媒介效能。为了揭示疾病过程的机制,进行了蛋白质组学分析,以评估感染 CHIKV 的小鼠组织中的宿主反应。对来自模拟和 CHIKV 感染组织的特定组织提取物的多个凝胶进行的比较分析表明,通过 35 种和 15 种分别属于不同类别(如应激、炎症、细胞凋亡、尿素循环、能量代谢等)的差异表达蛋白,对生理条件进行了剧烈的重新编程。来自肝脏和大脑。基于在 CHIKV 小鼠模型中获得的改变,可以定义 CHIKV 感染的大多数方面,如疾病严重程度、神经并发症、疾病易感性和免疫能力。这是首次采用蛋白质组学方法揭示基孔肯雅热发病机制中涉及的复杂途径的报告。

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