猪繁殖与呼吸综合征病毒GP5蛋白的结构与功能研究进展

Progress in Structure and Function of GP5 Protein of Porcine Reproductive and Respiratory Syndrome Virus

猪繁殖与呼吸综合征(Porcine Reproductive and Respiratory Syndrome,PRRS)是由猪繁殖与呼吸综合征病毒PRRSV引起的一种高度接触性传染病。作为一种RNA病毒,PRRSV的基因组存在广泛变异,其中以NSP2和ORF5基因变异为主。由于不同谱系毒株的ORF5有特征性的核苷酸序列,因此ORF5可用于PRRSV的分型。ORF5编码GP5蛋白,GP5蛋白含有多个表位,可与细胞受体作用,从而影响病毒的感染、复制。近年来,关于PRRSV的分子流行病学调查倾向于揭示不同毒株所特有的氨基酸突变。这些突变通常发生在GP5蛋白的信号肽编码区、非中和表位、中和表位和跨膜区。因此有研究将这些突变数据与病毒的毒力强弱、中和能力关联起来。而研究者尝试通过突变来推测GP5蛋白的构象或功能改变,从蛋白互作的结构基础层面来解释这种联系。由于GP5的三级结构并不能用传统的高分辨率冷冻电镜以及X射线晶体学方法观测,因此生物信息学方法成为相关研究的唯一选择。此外,GP5可用于基因工程疫苗的研制。综述了近年来关于GP5蛋白的生物信息学研究,并总结了GP5蛋白对病毒感染、复制、毒力、中和的影响,汇总了基于GP5的基因工程疫苗性能评测。

Porcine reproductive and respiratory syndrome(PRRS)is a highly contagious disease caused by porcine reproductive and respiratory syndrome virus(PRRSV).As an RNA virus,there are extensive variations in the genome of PRRSV,of which NSP2 and ORF5 genes are predominant.As the strains of different lineages have characteristic nucleotide sequences in ORF5,ORF5 can be used for the typing of PRRSV.ORF5 encodes the GP5 protein.GP5 protein contains multiple epitopes,which can interact with cellular receptors thus affect viral infection and replication.In recent years,molecular epidemiological investigations on PRRSV tend to reveal amino acid mutations unique to different strains.These mutations usually occur in the signal peptide coding region,non-neutralizing epitope,neutralizing epitope and transmembrane region of GP5 protein.Therefore,some studies have correlated these mutation data with the virulence and neutralization capacity of the virus.Some researchers tried to speculate about the conformational or functional changes in GP5 protein by mutation and explain this link from the structural basis of protein interaction.The tertiary structure of GP5 cannot be observed by traditional high-resolution cryo-EM and X-ray crystallography method,therefore,bioinformatics methods become the only option for related researches.In addition,GP5 can be used for the development of genetic engineering vaccines.This article reviews bioinformatics studies on GP5 protein in recent years,and summarizes the effects of GP5 protein on virus infection,replication,virulence and neutralization as well as the performance evaluation of GP5-based genetic engineering vaccines.