通过新的EV71抑制剂suramin靶点鉴定探索EV71病毒宿主相互作用

项目名称： 通过新的EV71抑制剂suramin靶点鉴定探索EV71病毒宿主相互作用

项目编号： No.31270204

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 艾德铭

作者单位： 山东大学

项目金额： 79万元

中文摘要： P2X拮抗剂suramin通过抑制EV71病毒进入宿主细胞而抑制EV71感染。P2X受体家族是重要的神经信号转导受体。EV71感染能引发神经源性肺水肿、心肺功能损伤、麻痹以及神经系统感染，可能与P2X受体功能异常或病毒通过P2X感染神经系统有关。我们将鉴定suramin抑制EV71感染的病毒和宿主靶点，来探索EV71感染中病毒和宿主细胞的相互作用。研究包括以下内容：1，测定P2X化合物探针、siRNA和亚型特异抗体对EV71感染的抑制作用，初步确定相关的P2X亚型；2，EV71不易感细胞中外源过量表达P2X能否介导EV71感染；3,耐药突变分析鉴定suramin的病毒靶点；4，suramin能否抑制SCARB-2、PSGL-1介导的EV71感染；5，EV71病毒对宿主细胞靶点蛋白信号转导和生理功能的影响。本项目将鉴定EV71病毒宿主相互作用的关键分子，并为EV71神经致病机理提供线索。

中文关键词： 肠道病毒71；抑制剂；suramin；靶点；受体

英文摘要： Our laboratory identified by chemical genetic screening that the P2X receptor antagonist suramin, an approved drug, inhibits EV71 replication in host cells at an early stage in the life cycle. There are seven P2X receptors, all of which are ligand-gated cationic receptors, which respond to extracellular ATP and are important in neuronal signal transduction. EV71 infection of the Central Nervous System infection causes neurogenic pulmonary edema, cardiopulmonary dysfunction, paralysis, CNS infection and inflamation. The pathophysiological mechanisms leading up to neurological symptoms are not understood. We believe that P2X receptors could play a crucial role in this process by facilitating viral replication at the cellular level and triggering P2X signalling events that lead to cardiopulmonary dysfunction. Our project aims at identifying key factors involved in EV71 entry and EV71 viral-cell interaction through the identification of both suramin viral and cellular target proteins as well as the effect of EV71 infection on cellular signalling through P2X receptors. The project will include the following studies: 1. Analyze which P2X subtype/subtypes are involved in EV71 entry by blocking P2X receptor with chemical probes, P2X subtype specific antibodies, and downregulation of P2X surface expression by siRNA; 2. A

英文关键词： EV71；inhibitor；suramin；target；receptor