寨卡病毒感染导致小颅畸形的发病机制与防治研究

大脑发育是一个精确调控的过程，大脑发育异常可导致小颅畸形等疾病。寨卡病毒在全球范围内已播散蔓延到72个国家或地区，我国也面临输入并引起流行的风险。寨卡病毒感染被认为与南美大规模出现的新生儿小颅畸形有关，国际卫生组织（WHO）为此在2016年2月宣布寨卡病毒感染为“国际关注的突发公共卫生事件”。我们和其他团队通过建立小鼠感染模型，首次确定寨卡病毒感染可以直接导致小颅畸形，但国际上有关寨卡病毒感染的发病机制研究才刚刚开始。本项目将通过建立和完善不同的动物模型，着重研究并解决两个关键科学问题：寨卡病毒感染导致小颅畸形的分子和细胞学机制是什么？能否进行有效防治？我们将综合运用多学科研究手段和先进技术，力争在分子细胞水平和动物整体水平，阐明寨卡病毒导致小颅畸形的发病机制，为小颅畸形的防治提供理论依据，同时，进一步推动防治寨卡病毒感染药物（抗体）和疫苗的筛选和验证，促进相关产品向临床转化。

Brain development is a precisely controlled process. Disturbance of brain development would lead to brain disorders such as microcephaly. Zika virus (ZIKV) has been spread to more than 72 countries or areas and there is chance for ZIKV to spread to China. ZIKV infection is thought to be associated with the large-scale neonatal microcephaly emerging in South America countries. Due to this global threat, the International Health Organization (WHO) declared a public health emergency of international concern on Feb. 2016. Through the establishment of mouse infection models, we and other teams established, for the first, the direct link between ZIKV and microcephaly. However, the study of the related pathogenesis has just begun in the world. This project will try to solve two key scientific questions by establishing and improving new microcephaly animal models: 1. What is the molecular and cellular mechanism of microcephaly caused by ZIKV infection? 2. Are there effective ways to prevent or treat microcephaly caused by ZIKV infection? We will use a combination of multidisciplinary research tools and advanced technology, and strive to explore the pathogenesis of microcephaly caused by ZIKV infection at both molecular and cellular levels, and in the overall whole animal level, in order to provide a theoretical basis for the prevention and treatment of microcephaly. Meanwhile, we will perform the translational medicine study in the screening and validation of drugs (antibodies) and vaccines for ZIKV infection.