坦布苏病毒是黄病毒科成员之一。该病毒主要感染水禽，但其致病机制尚不明确。前期研究发现，坦布苏病毒及其非结构蛋白NS1和NS4B均能够抑制鸭STING对IRF7和IFN-β启动子的激活及转录，从而抑制宿主细胞I型干扰素的表达。因此，本项目拟研究坦布苏病毒非结构蛋白与鸭STING互作抑制I型干扰素表达的分子机制。首先通过qPCR、WB等方法确定病毒对STING及其下游分子转录和表达的影响。随后过表达或敲减STING后，分别共表达NS1、NS4B蛋白及其截短体，确定NS1和NS4B蛋白能否抑制鸭STING及其下游分子的转录和表达。最后利用免疫共沉淀和激光共聚焦等技术解析NS1和NS4B蛋白全长及其截短体与鸭STING能否互作、互作的区域及其细胞内定位。最终，阐明坦布苏病毒非结构蛋白与鸭STING互作抑制I型干扰素表达的分子机制，这将为进一步了解鸭坦布苏病毒感染的分子机理提供研究数据。

Tembusu virus is a member of Flaviviridae that mainly infects waterfowls. However, its pathogenesis is not fully understood. Our previously study found that the non-structural protein NS1 and NS4B of Tembusu virus and the virus itself could suppress the activation and transcription of IRF7 and IFN-beta promoters by duck STING (Stimulator of the interferon gene). Therefore, this study intends to understand the molecular mechanism of the interaction between Tembusu virus non-structural protein and duck STING that suppressing the expression of type I interferon. Firstly, the transcription and expression of duck STING and its downstream signaling molecules in DEF (Duck embryo fibroblast) will be determined by qPCR and WB (Western blot). Subsequently, whether the NS1 and NS4B proteins could suppress the transcription and expression of duck STING and its downstream signaling molecules will be confirmed by overexpression or knockdown of duck STING in DEF or co-expressed with NS1, NS4B proteins and their truncates. At last, whether the NS1, NS4B proteins and their truncates could interact or intracellular co-localize with duck STING will be analyzed by immunoprecipitation and confocal laser scanning microscopy. Finally, the molecular mechanism of interaction between Tembusu virus non-structural protein and duck STING suppressing the expression of type I interferon will be elucidated. This study will be useful for further elucidating the molecular mechanism of duck Tembusu virus infection.