埃可病毒18型属于肠道病毒B组，是引起儿童病毒性脑炎/脑膜炎的重要病原，近年在世界多地暴发，严重威胁儿童健康。本课题组报道了该病毒在国内所致儿童脑炎/脑膜炎的暴发。目前，埃可病毒18型感染入侵相关受体尚不明确，阻碍了其致病机制及药物研究。本研究基于课题组前期获得的毒株，应用CRISPR-Cas9人基因组表面蛋白基因文库筛选系统，对人细胞所有表面蛋白编码基因进行高通量筛选研究，获得了3个候选受体编码基因；拟进一步通过单基因敲除及重建后感染实验，病毒衣壳蛋白与受体结合实验、单抗阻断实验等进行验证及功能研究，最终确定该病毒感染入侵过程中的受体；并应用埃可病毒6、11、14、19、30、33型等进行受体敲除后感染实验，分析所筛选受体是否为多种血清型埃可病毒共用受体。该研究将为埃可病毒18型入侵感染分子机制研究提供基础，为药物及疫苗的研发提供新靶点，对该病毒引起的儿童脑炎/脑膜炎的防治具有重要意义。

Echovirus 18 belongs to enterovirus B group, is one of the most important pathogens of viral encephalitis/ meningitis in children. There were several outbreaks of viral encephalitis/meningitis caused by echovirus 18 all over world in recent years, which was a serious threat to the health of children. We’ve reported an outbreak of encephalitis/ meningitis caused by echovirus 18 in children of Hebei province at 2015. To date, the receptor for echovirus 18 infecting cells is still not clear, which is an obstacle to the research of its pathogenic mechanism and drug development. Based on the strains of echovirus 18 obtained in our previous study，using CRISPR-Cas9 human genomic library screening system, we have finished the high-throughput screening study of all the surface membrane protein coding genes of the human cell and found three candidate receptor genes. In this study, we plan to explore and determine the host receptor for echovirus 18 invading cells by using single candidate receptor gene knockout test, infection experiment after candidate receptor gene knock in, binding assay for viral capsid protein and receptor, monoclonal antibody blocking experiment and so on. Finally, we will further investigate whether the receptor is a common receptor for other serotype echoviruses, such as E6, 11, 14, 19, 30, 33 and so on. The results of this study will provide a basis for further study on molecular mechanism of echovirus 18 infection。 It will provide new targets for drug and vaccine development. This study is of great significance for the prevention and treatment of encephalitis / meningitis in children caused by Echovirus 18.