狂犬病病毒（Rabies virus, RABV）为弹状病毒科狂犬病病毒属成员，其基质蛋白（M蛋白）是一种多功能蛋白，在调控病毒转录与复制、促进病毒粒子组装和出芽、诱导细胞凋亡和影响病毒致病力方面发挥着重要作用。本研究在我们初步发现过表达辅伴侣蛋白BAG3抑制RABV复制以及BAG3与病毒M蛋白相互作用的前期工作基础上，借助病毒学、分子生物学、细胞生物学以及生物化学等技术，确定BAG3在RABV感染过程的具体作用方式。同时采用串联亲和纯化与质谱联用方法筛选并鉴定在病毒M蛋白参与的情况下与BAG3相互作用发生增强或减弱的宿主蛋白，借助上述技术分析这些宿主蛋白对BAG3调控RABV复制的作用，阐明BAG3在RABV感染过程中作用的分子细节。本研究对病毒M蛋白与BAG3相互作用在RABV复制机制中的深入研究有助于抗RABV新药物靶标的研究开发，具有重要的科学意义及理论价值。

Rabies virus (RABV) is a member of the genus Lyssavirus belonging to the family Rhabdoviridae, and its matrix protein is a multifunctional protein, which plays an important role in regulating viral transcription and replication, promoting the assembly and budding of virus particles, inducing cell apoptosis and affecting virus virulence. In this study, based on our preliminary findings of RABV replication inhibited by overexpressing the co-chaperone BAG3, and the interaction between RABV M protein and BAG3, techniques of virology, molecular biology, cell biology and biochemistry were used to determine the function of BAG3 during RABV infection. In addition, a tandem affinity purification coupled with mass spectrometry approach were used to screen and identify the host proteins which exhibited an increased or reduced interaction with BAG3 in the presence of RABV M protein, and the effect of these host proteins on the RABV replication regulated by BAG3 was further analyzed by using the above techniques, which elucidated molecular details of the role of BAG3 during RABV infection. The study on the interaction between RABV M protein and BAG3 in the mechanism of RABV replication is useful for the research and development of new drug targets for RABV, which has important scientific significance and theoretical value.