狂犬病病毒结构蛋白研究进展

Research progress in structural proteins of rabies virus

狂犬病病毒(rabies virus,RABV)是狂犬病的最主要病原体,属于弹状病毒科(Rhabdoviridae)狂犬病病毒属(Lyssavirus),是有包膜的单股负链RNA病毒。RABV基因组编码核蛋白(nucleoprotein,N)、磷蛋白(phosphoprotein,P)、基质蛋白(matrix protein,M)、糖蛋白(glycoprotein,G)和依赖于RNA的RNA聚合酶(RNA-dependent RNA polymerase,RdRp)共五种结构蛋白。N蛋白主要在病毒的转录与复制过程中发挥重要作用,多用于诊断和病毒鉴定;P蛋白可与一些宿主的蛋白伴侣相互作用,颠覆抗病毒信号通路,影响RABV的致病性;M蛋白则在调节病毒转录与复制之间的平衡方面起重要作用;G蛋白是诱导中和抗体的靶点,融合前其三聚体结构的解析、融合环对G蛋白成功三聚体化和构象稳定的影响,以及有效和广谱中和抗体表位的可视化等为研发广谱疫苗提供了依据;而RdRp蛋白主要催化病毒RNA进行转录。近年结构蛋白晶体结构的解析、相关功能位点以及与小分子相互作用等方面的研究,有助于研究者更好地了解RABV的致病机理、寻找有效抗病毒药物靶点以及设计更广谱的疫苗。

Rabies virus(RABV)belonging to the Rhabdoviridae family and the Lyssavirus genus is the main pathogen of rabies and is a single stranded RNA virus with an envelope.The RABV genome encodes five structural proteins:nucleoprotein(N),phosphoprotein(P),matrix protein(M),glycoprotein(G),and RNA dependent RNA polymerase(RdRp).The N protein mainly plays an important role in the transcription and replication process of viruses,which is often used for diagnosis and virus identification;P protein can interact with some host protein partners,disrupt antiviral signaling pathways,and affect the pathogenicity of RABV;M protein plays an important role in regulating the balance between viral transcription and replication;as a target for inducing neutralizing antibodies,the trimeric structure analysis of G protein before fusion,the influence of fusion rings on successful trimerization and conformational stability,and the visualization of effective and widespread neutralizing antibody epitopes provide a basis for the development of broad-spectrum vaccines.The RdRp protein mainly catalyzes the transcription of viral RNA.In recent years,the analysis of the crystal structure of structural proteins,the discovery of related functional sites,and the interaction with small molecules have helped researchers better understand the pathogenicity of RABV,search for effective antiviral drug targets,and design broad-spectrum vaccines.