寨卡病毒因与小头症密切关联而备受关注，阐明其独特的致病机制和研发疫苗迫在眉睫。MicroRNA（miRNA）是一类组织特异性表达的具有重要调控功能的非编码小RNA。我们的前期研究发现，寨卡病毒能靶向胎鼠神经祖细胞和胶质细胞，导致皮层发育异常和小头畸形。本研究首先通过深度测序分析寨卡感染神经祖细胞、胶质细胞及胎脑中miRNA表达谱特征，鉴定特异细胞中高丰度表达的miRNA及其潜在功能；同时利用建立的寨卡病毒反向遗传学技术平台，构建一系列携带脑组织特异miRNA 靶序列的重组寨卡病毒，系统评估其体外复制能力，筛选丧失神经毒力显著降低的减毒株，进一步评价其在动物体内导致的细胞和体液免疫反应水平，并完成其对寨卡攻击的免疫保护效果评价。本研究将能够鉴定出与寨卡病毒神经嗜性密切相关的miRNA，获得神经毒力显著降低的重组寨卡减毒疫苗株，对于深刻理解寨卡病毒与宿主相互作用及新型疫苗研发具有重要意义。

The global spread of Zika virus (ZIKV) and unexpected link to birth defect urge study of ZIKV pathogenesis and the rapid development of a safe and effect vaccine. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a pivotal role in the regulation of posttranscriptional gene expression in eukaryotic organisms. In previous studies, we found that ZIKV replicated efficiently in the mouse embryonic brain by mainly targeting neural progenitor cells and caused microcephaly. In this study, by using RNA-seq, microarray analysis and Northern blot we will characterize the miRNA production pattern in ZIKV-infected neural cells including neural progenitor cells, human embryonic stem cells and neurons. A set of miRNAs with highly expression in these cells will be identified. Next, we will insert neural specific miRNAs target sites into ZIKV genome by using reverse genetics to generate recombinant ZIKVs (miRNA-ZV), and determine their replicative properties in neural and non-neural cells. Further, the tissue tropism of miRNA-ZVs will be explored in mice, and protective efficiency of miRNA-ZVs will be evaluated in the mouse model of ZIKV infection. Our study will identify a set of miRNAs close related with ZIKV infection in neural cell lines, and elucidate the underlying mechanism responsible for miRNA-mediated attenuation of the miRNA-ZIKV. The findings in our study will provide insights into understanding ZIKV-host interactions. The live attenuated neurovirulence miRNA-ZV will deserve further development as a ZIKV vaccine candidate.