RNA病毒激活炎症反应调控血液屏障的分子机制

RNA viruses (influenza A virus, Zika virus, Dengue virus, HIV-1, Ebola virus, and enterovirus) are serious threats to human life and health. The host inflammatory reactions can quickly and effectively remove the virus and play a vital role in viral infections. However, the disorder and excessive inflammatory responses can cause organ damage and serious disease. Thus, it is very important to determine the mechanisms underlying viral infections induce inflammation, leading to the development of diseases. Enterovirus 71 (EV71) infection causes hand, foot and mouth disease (HFMD) as well as central nervous system (CNS) diseases; Zika virus (ZIKV) infection causes neonatal microcephaly and male sterility; but the mechanism of virus infections and pathogenses are still largely unclear. This project intends to study 2 viruses (EV71 and ZIKV) in order to elucidate the molecular mechanism of RNA viruses activate inflammations; focue on 3 diseases (meningoencephalitis, microcephaly and male sterility) to determine the activation effect of inflammation on blood barrier permeability to RNA virus; and evaulate 4 proteins (interleukin-1, matrix metalloproteinases, epidermal growth factor, platelet-derived growth factor) to reveal the mechanisms by which viruses activate inflammatory response to regulate blood barrier and lead to disease developmment. Our aim is to provide theoretical basis and technical support for the prevention and treatment of inflammation and related viral diseases.

寨卡病毒、肠道病毒、流感病毒、登革病毒、埃博拉病毒等RNA病毒感染严重威胁人类生命健康；机体免疫应答和炎症反应能有效的清除病毒，在抗病毒感染中起至关重要的作用；但失调和过度的炎症反应，能导致组织器官损伤、产生严重疾病；研究病毒感染激活炎症反应导致相关疾病的分子机制，意义重大。肠道病毒71型EV71感染通常引起手足口病HFMD，还可感染中枢神经系统CNS导致无菌性脑膜炎、脑干脑炎、神经源性肺水肿等并发症，极少数患者病情危重、甚至死亡。寨卡病毒ZIKV感染通常引起寨卡热、格林-巴利综合征GBS和自身免疫病，还可导致新生儿小头症和雄性不育。但是EV71和ZIKV感染导致相关疾病的机制尚未阐明。本项目在课题组前期研究工作的基础上，结合国内外研究进展和发展前沿，以EV71和ZIKV 2种病毒为对象，阐明RNA病毒激活炎症反应的机制；以脑膜脑炎、小头症、雄性不育3种疾病为核心，确定RNA病毒激活炎症反应对血液屏障通透性的影响；以白介素-1β、基质金属蛋白酶、表皮生长因子、血小板衍生生长因子4种蛋白为重点，揭示病毒激活炎症反应、调控血液屏障、导致疾病的机制，旨在为防治炎症及病毒病提供理论依据。

寨卡病毒、肠道病毒、流感病毒、登革病毒、埃博拉病毒等RNA病毒感染严重威胁人.类生命健康；机体免疫应答和炎症反应能有效的清除病毒，在抗病毒感染中起至关重要的.作用；但失调和过度的炎症反应，能导致组织器官损伤、产生严重疾病；研究病毒感染激.活炎症反应导致相关疾病的分子机制，意义重大。肠道病毒71型EV71感染通常引起手足口.病HFMD，还可感染中枢神经系统CNS导致无菌性脑膜炎、脑干脑炎、神经源性肺水肿等并.发症，极少数患者病情危重、甚至死亡。寨卡病毒ZIKV感染通常引起寨卡热、格林-巴利.综合征GBS和自身免疫病，还可导致新生儿小头症和雄性不育。但是EV71和ZIKV感染导致.相关疾病的机制尚未阐明。本项目在课题组前期研究工作的基础上，系统性的阐述EV71激活炎症反应、突破小鼠血脑屏障、感染小鼠大脑、导.致脑膜脑炎的分子机制，确定 ZIKV激活炎症反应、突破孕鼠胎盘屏障、感染胎鼠大脑、导.致小头症的分子机制，阐述RNA病毒调控炎症反应和血液屏障导致疾病的分子机理.了为防治炎症及病毒.病提了供理论依据及潜在靶标。