ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究

Id1 (inhibition of DNA binding 1) protein belongs to the helix-loop-helix (HLH) family of transcription factors, which controls a wide range of developmental and cellular processes by inhibiting the activity of the basic helix-loop-helix (bHLH) family of transcription factors. At present most researchers are focusing on the ID1 functions in promoting tumorigenesis and maintaining embryonic stem cell self-renewal and pluripotency. But few papers have been reported about the ID1 function in immune response during virus infection. Here we reported for the first time that FMDV could induce rapid expression of the ID1 protein during the early period of infection, and then decreased with the infection time. Most importantly, compared with the control, BMP4 (Bone morphogenetic protein 4) treatment not only induced higher expression of ID1 during FMDV infection, but also significantly inhibited the replication of virus, which showed the possible involvement of ID1 function during virus infection. Further investigation of the underlying mechanism will shed light on the prevention and vaccination of foot and mouth disease.

ID1（Inhibitor of DNA binding 1）蛋白是一个具有螺旋-环-螺旋 （Helix-Loop-Helix）结构域的转录因子，参与生物体许多生长发育进程的调控。目前关于ID1在促进肿瘤的增殖和迁移及抑制胚胎干细胞分化中的作用机制研究较多，但是ID1在口蹄疫病毒感染过程中的作用机制尚未见报道。我们的前期研究工作表明，口蹄疫病毒感染细胞可诱导ID1的迅速表达，随着感染时间的延长逐渐降低至本底水平；骨形态发生蛋白BMP4（Bone morphogenetic protein 4）不但能诱导ID1的高表达，而且可抑制病毒在细胞内的复制。所以我们推测口蹄疫感染细胞过程中诱导ID1调控的免疫反应的启动，且BMP4对口蹄疫病毒在细胞内复制的抑制也是通过ID1介导的免疫反应。本课题拟在前期的工作基础上深入研究ID1在病毒感染过程中的作用机制，为口蹄疫的防控及疫苗制备提供理论基础。

本项目的研究目标是利用分子生物学、生物化学、细胞生物学、免疫学及生物信息学等手段深入研究ID1在口蹄疫病毒感染过程中的作用机制。阐明病毒感染过程中ID1介导的天然免疫信号通路以及病毒结构蛋白或者非结构蛋白调控ID1表达的作用机制，从而为口蹄疫防控及疫苗研制提供理论基础。.通过试验，本项目证明ID1与转录因子FOXO1结合并抑制其转录活性，从而促使IRF3基因的表达及干扰素的产生，抑制口蹄疫病毒的复制。而口蹄疫病毒感染促使ID1的泛素化降解，进而的研究表明，口蹄疫病毒的2A2B蛋白、2C及3C蛋白均可抑制ID1蛋白的表达，从而有利于病毒的复制。另外，本项目还通过miRNA Array及生物信息学分析筛选出调控口蹄疫病毒复制的miRNAs3个，分别是miRNA-1307、miRNA-4331-5p及miRNA-4334-5p，其中miRNA-4334-5p通过ID1蛋白调控干扰素信号通路从而有利于口蹄疫病毒的复制。.相关研究结果分别发表于FEBS Journal，Virology，Virus Research和Genes杂志；申请国家发明专利5项，获得授权2项；培养博士研究生1名，硕士研究生2名。