寨卡病毒感染调控胎盘屏障的分子机制

In 2016, ZIKV has been reported as an international public health emergency and aroused widespread concern around the world due to the link of ZIKV infection to the neurological complications and the congenital birth defects. Recognition of virus infection by host innate immune system is essential for the effective defense to control virus replication. But the excessive inflammatory response can help virus cause the disease. The detailed mechanism by which ZIKV infection modulate and pass the placenta barrier to induce the microcephaly is still unknown. In our previous study, we have indicated that ZIKV infection can induce NLRP3 inflammasome and ZIKV NS5 protein can bind with NLRP3 to facilitate the inflammasome complex assembly. What’s more, ZIKV infection in mice activates IL-1β secretion, modulates and passes the blood brain barrier and infects the mice brain. Thus, in this project, we focus on the ZIKV-induced microcephaly to determine the activation effect of inflammasome on placenta barrier to ZIKV. We evaluate IL-1β to reveal the mechanism by ZIKV modulate and pass the placenta barrier and then infect the fetus to induce microcephaly. Our aim is to provide important theoretical foundation for the prevention and treatment of ZIKV-induced disease.

寨卡病毒（ZIKV）因为会引起神经学并发症以及新生儿缺陷，在2016年被报道成为国际性的突发公共卫生事件，引起了全世界广泛的关注。天然免疫系统经过识别病毒入侵启动宿主免疫抵抗病毒复制，但是过度的炎症反应同样会帮助病毒引起疾病。寨卡病毒如何调控并通过胎盘屏障，从而引起小头症的具体机制一直不太清楚。我们前期的研究结果表明寨卡病毒感染可以激活NLRP3炎症小体，寨卡病毒的NS5蛋白可以与NLRP3结合从而帮助NLRP3炎症小体组装。随后，我们还发现寨卡病毒感染小鼠引起IL-1β产生，帮助寨卡病毒感染穿过血脑屏障，感染小鼠大脑。因此在此项目中，我们聚焦寨卡病毒感染引起的小头症，阐述在病毒感染过程中激活炎症小体从而对胎盘屏障的调节。我们以IL-1β为核心，揭示寨卡病毒通过胎盘屏障进而引起胚胎小头症的具体机制。旨在为防治寨卡病毒感染引起的疾病提供理论依据。

寨卡病毒（ZIKV）因为会引起神经学并发症以及新生儿缺陷，在2016年被报道成为国际性的突发公共卫生事件，引起了全世界广泛的关注。寨卡病毒如何调控并通过胎盘屏障，从而引起小头症的具体机制一直不太清楚。我们前期的研究结果表明寨卡病毒感染可以激活NLRP3炎症小体，寨卡病毒的NS5蛋白可以与NLRP3结合从而帮助NLRP3炎症小体组装。随后，我们还发现寨卡病毒感染小鼠引起IL-1β产生，帮助寨卡病毒感染穿过血脑屏障，感染小鼠大脑。本项目我们发现寨卡病毒感染释放大量ATP之后通过paxillin蛋白激活NLRP3的具体机制，找到层粘连蛋白受体LAMR1与寨卡病毒E蛋白结合抑制寨卡病毒的复制，随后合成LAMR1的20aa多肽，可以抑制寨卡病毒入侵细胞，抑制寨卡病毒复制，缓解寨卡病毒感染引起的小头症，为防治寨卡病毒感染引起的疾病提供理论依据