狂犬病是由狂犬病病毒（RABV）引起的以侵害中枢神经系统为特征的高度致死性人兽共患传染病，一旦出现临床症状，死亡率高达100%，寻找有效的抗RABV药物并阐明其作用机制是亟需解决的问题。我们前期研究发现，PGG可有效抑制RABV的复制并挽救病毒感染的小鼠，同时，PGG也可显著抑制由RABV诱导的STAT3激活及IL-6释放，但PGG调控STAT3通路发挥抗RABV作用的分子机制尚不清楚。本课题采用CRISPR-Cas9、ELISA、荧光素酶报告基因系统、miRNAs array及反向遗传系统等技术，明确STAT3通路在RABV感染复制中的作用，RABV诱导STAT3通路激活的关键蛋白，以及PGG逆转STAT3通路发挥抗病毒作用的分子机制，从STAT3的角度揭示RABV的致病机制，阐明PGG调控STAT3信号通路介导抗RABV作用的分子机制，为改善狂犬病的治疗提供新的救治药物和理论依据。

Rabies virus (RABV) is a frightening virus which causes fatal encephalomyelitis in humans and mammals. Numerous therapies and drugs have been discovered to treat the rabies, although they are not always effective, and the mortality is almost 100% once the symptom appears. Our previous studies have reported pentagalloylglucose (PGG), a natural hydrolysable phenolic tannic, possesses a significant anti-RABV effect in vitro and in vivo, our preliminary experiments also implied that the efficacy of PGG is probably associated with the activity of STAT3 signaling pathway However, the convictively underlying mechanism of PGG to RABV is urgently deserving further studies. In this study, the CRISPR-Cas9, ELISA, luciferase reporter assay, miRNAs array, direct immunofluorescence, and the reverse genetics system are performed to clarify the crucial roles of STAT3 pathway in regulating the replication of RABV in host cells, and the regulation mechanisms by which PGG reverses STAT3 pathway and exert its anti-RABV efficacy. This project would provide strong evidence that STAT3 pathway appears to be mainly responsible for the virus replication and inflammatory factor production that occurs during RABV infection, and PGG could work as an effective drug to reverse the response and rescue the infected mouse, which could also be developed to a potential candidate for RABV therapy.