PCP4L1通过上调TRIM72抑制狂犬病病毒复制的分子机制

狂犬病（Rabies）是由狂犬病病毒（Rabies virus，RABV）引起的一旦发病死亡率几乎为100%的一种重要人畜共患病，至今仍未有有效的治疗手段。申请人的前期研究结果发现lncRNA EDAL可以促进抗病毒多肽PCP4L1的转录表达并且PCP4L1可以促进TRIM72的转录表达。本项目拟通过在神经元细胞中过表达或敲除TRIM72研究其对RABV增殖的影响；利用蛋白-蛋白互作的方法筛选并鉴定出可能与TRIM72互作的RABV蛋白；利用分子对接的方式研究互作蛋白间精确的结合位点；利用反向遗传操作技术构建过表达TRIM72的重组RABV并进行小鼠攻毒实验分析TRIM72对RABV致病性的影响；最终阐释PCP4L1通过调控TRIM72抑制RABV增殖的分子机制，为治疗狂犬病药物靶点的筛选提供新的思路。

Rabies is an important zoonosis caused by rabies virus, which has almost 100% mortality rate, and there is still no effective treatment. The applicant's previous studies found that lncRNA EDAL can promote the transcriptional expression of antiviral polypeptide PCP4L1, and PCP4L1 can promote the transcriptional expression of TRIM72. This project aims to study the effect of over-expression or knockout TRIM72 in neuronal cells on RABV proliferation; the RABV proteins that may interact with TRIM72 will be screened and identified by protein-protein interaction assays; the precise binding sites between interacting proteins will be studied by molecular docking; the recombinant RABV of over-expression TRIM72 will be constructed by reverse genetic manipulation and the effect of TRIM72 on the pathogenicity of mice will be analyzed; finally, the detailed molecular mechanism of PCP4L1 inhibition of RABV proliferation by regulating TRIM72 will be explained, which will provides new ideas for the screening of rabies drug targets.