干扰素及其诱导的抗病毒免疫反应在病毒感染早期发挥着非常重要的抗病毒作用，而病毒为实现感染往往能利用其编码的蛋白通过不同的机制拮抗宿主的Ⅰ型干扰素反应。研究表明寨卡病毒编码的多个病毒蛋白具有拮抗Ⅰ型干扰素的功能，但是其具体的分子机制还有待进一步阐明。我们的前期实验结果表明寨卡病毒感染之后并不能诱导IRF3入核；通过构建不同病毒蛋白的表达质粒，我们发现单独表达的NS4A蛋白能够抑制仙台病毒诱导的Ⅰ型干扰素反应和IRF3的入核，提示寨卡病毒NS4A蛋白能够通过抑制IRF3的激活从而拮抗宿主的I型干扰素反应。在前期结果的基础上，本研究拟采用定点突变、报告基因实验、激光共聚焦、WB和免疫共沉淀、RNA干扰等实验深入探索寨卡病毒NS4A蛋白拮抗Ⅰ型干扰素反应的分子机制。本研究有望进一步补充和深入阐明寨卡病毒抑制天然免疫的分子机理，为新型抗病毒药物靶标的发现提供理论依据和新思路。

Interferon (IFN) and IFN-induced antiviral responses are the first line of defense against viral infections, and play a vital role in the early host response. Viruses have evolved multiple mechanisms to combat and evade the IFN response during infection. Previous studies have shown that several viral proteins of Zika virus (ZIKV) could antagonize the type I IFN response. However, the underlying molecular mechanisms behind this observation need further elucidation. Our preliminary results showed that ZIKV infection prevents the nuclear translocation of IRF3, which is essential for the induction of interferon. Additionally, ZIKV NS4A protein inhibits the SeV-induced type I interferon response and nuclear translocation of IRF3, suggesting that NS4A antagonizes the type I IFN response via IRF3. We propose to explore the NS4A-mediated inhibition of the type I IFN response by utilizing the site-directed mutagenesis, reporter gene assay, indirect immunofluorescence and confocal microscopy, western blot, co-immunoprecipitation and RNA interference. The results from our study will add to our understanding of the pathogenesis and immune evasion mechanisms of ZIKV, providing a theoretical basis and new strategies for the development of antiviral drugs.