IER3蛋白调控细胞内吞通路抑制牛病毒性腹泻病毒复制的作用机制研究

牛病毒性腹泻病毒（BVDV）严重影响全球畜牧业的发展，也是牛源生物制品常在污染源。病毒的复制依赖宿主细胞因子发挥辅助作用，寻找参与病毒复制的宿主细胞通路及关键蛋白，将利于阐明病毒致病机制，为疫病防治提供新靶标。本项目组前期发现早期应答基因3（IER3）敲除显著性抑制BVDV复制，IER3敲除后胞浆中呈现大量的内吞体囊泡，使用邻近标记技术和蛋白质谱捕获与IER3互作的蛋白主要富集于细胞内吞途径；而IER3如何参与调控细胞内吞途径？IER3是否通过调控细胞内吞抑制BVDV复制？IER是否影响BVDV体内复制？尚未见研究报道。本研究将基于前期基础，全面探索IER3与细胞内吞途径重要蛋白互作情况、解析IER3调控细胞内吞影响BVDV复制的分子机制、探明IER3影响BVDV体内复制的作用，为揭示BVDV与宿主细胞相互作用和BVDV致病机制等提供理论依据，也为研发BVDV防控技术提供新型作用靶点。

Bovine viral diarrhea virus (BVDV) has seriously affected the development of livestock and poultry industry worldwide, and is also a common source of contamination of bovine biological products. Virus replication depends on the host cell factor played an auxiliary role, and finding the host cell pathway and important factors involved in virus replication will contribute to clarify the pathogenesis of the virus and provide novel targets for disease control. The previous findings of our project team showed that early response gene 3 (IER3) knockout significantly inhibited the replication of BVDV. After the knockout of IER3, a large number of endocytosis vesicles presented in the cytoplasm. The proteins interacted with IER3 screening with the proximity labelling technology and protein mass spectrometry were mainly enriched in the endocytosis pathway. How does IER3 participate in the regulation of endocytosis? Does IER3 inhibit BVDV replication by regulating endocytosis? Does IER3 affect the replication of BVDV in vivo? However, there is no the systemic reports with regard to these scientific problems. Based on the previous findings, this study will comprehensively explore the interaction between IER3 and important proteins of endocytosis pathway, analyse the molecular mechanism of IER3 regulating endocytosis affecting BVDV replication, and investigate the effect of IER3 on BVDV replication in vivo. The results will provide theoretical basis for the interaction between BVDV and host cells and the pathogenesis of BVDV, and also provide a novel target for the research and development of BVDV prevention and control technology.