大连地区腮腺炎病毒G基因型全基因组特征

Genomic characteristics of mumps virus genotype G in Dalian

摘要:

目的 腮腺炎病毒(mumps virus, MuV)是引起流行性腮腺炎的病原体，目前国内广泛流行的为F基因型，局部地区出现G基因型，且存在逐渐扩大趋势。为了解国内G基因型MuV全基因组的基因特征，本研究选择辽宁大连地区分离到的2株腮腺炎G基因型毒株进行分析。方法 对2株腮腺炎毒株进行全基因组测序，依据世界卫生组织(World Health Organization, WHO)各基因型参考毒株序列确认毒株型别，同时开展分子生物学分析，对腮腺炎各基因型别间及G基因型内差异进行比较；结合我国其他地区G基因型毒株的基因组序列信息，分析我国G基因型MuV的全基因组特点及其与现有疫苗株的遗传距离及关键抗原位点变异情况。结果 本研究分离毒株为G基因型，与已划分的12个基因型间核苷酸差异为4.2%-6.9%，与A基因型差异最大；蛋白编码基因中，SH基因变异最大，NP、M和L基因相对保守，P基因、F基因、HN基因型间差异较大。本研究分离的G基因型毒株与GenBank数据库国内分离株江苏省毒株(Jiangsu.CHN/22.13/2)亲缘关系最近，与同为辽宁地区分离株存在差异。在关键抗原表位中，本研究分离的G基因型毒株与疫苗株相比在HN蛋白少了aa 12-14位N-糖基化位点，但多了aa 464-466位N-糖基化位点，在中和表位中，G基因型毒株与A基因型疫苗株差异较大，提示这些氨基酸位点的变异很可能会潜在地降低腮腺炎疫苗株对MuV野毒株的交叉保护作用，而F蛋白虽然有氨基酸差异，但功能区域较为保守。结论 本研究详细分析了大连地区G基因型毒株的基因型别特征，与国内G基因型毒株及参考毒株整体较为相似，存在部分差异位点，但与全球范围内使用的疫苗株(A基因型)差异较大。本研究提示未来需持续开展国内腮腺炎病例监控，对流行病学和病毒学特征进行分析，为国内腮腺炎病毒溯源、传播途径及免疫策略制定提供方向。

关键词:腮腺炎病毒;G基因型;全基因组;基因特征

Abstract:

Objective Mumps virus (MuV) is the causative agent of mumps. Nowadays, genotype F is widely prevalent in China, while genotype G appears in localized areas and is exhibiting a trend of gradual expansion. To understand the genetic characteristics of genotype G strains in China, we selected two genotype G MuV strains that were isolated from Dalian, Liaoning for analysis.Methods The whole genomes of the two strains were sequenced, and the genotypes were determined according to the WHO reference strains. Furthermore, we compared the molecular characteristics among different genotypes and within genotype G. By comparison with the sequences of genotype G strains in other areas of China, we analyzed the features of genotype G MuVs in China, as well as the genetic distance and variations of key antigenic sites between the wild-type genotype G strains and the existing vaccine strains.Results The strains isolated in this study both belonged to genotype G, and they showed the nucleotide differences ranging from 4.2% to 6.9% from other 12 genotypes, with the greatest divergence from genotype A. Among the protein coding genes, the SH coding gene exhibited the largest variation, while the NP, M, and L coding genes were conserved. The P, F and HN coding genes demonstrated significant differences among different genotypes. The genotype G strains isolated in this study were closely related to the strain isolated in Jiangsu Province (Jiangsu.CHN/22.13/2), while they were distinct from the strains previously isolated in Liaoning Province. The genotype G strains isolated in this study lacked a N-glycosylation site (aa 12-14) but gained a N-glycosylation site (aa 464-466) in the key epitope of HN protein. In addition, the genotype G strains showed considerable differences in terms of neutralizing epitopes from the genotype A vaccine strain. These differences suggested that the mutations of these sites may potentially reduce the cross-protection effects of vaccine strains against wild-type MuV strains. Although there were some mutations in F protein, the functional region was conserved.Conclusion This study details the genotypic characteristics of genotype G MuVs in Dalian, highlighting their high similarities to the genotype G strains in China and the WHO reference strains, while underscoring significant differences from the genotype A vaccine strain used worldwide. These findings suggest the necessity of continuous surveillance of MuV strains in China and further studies of their epidemiology and virology, which could provide references for tracing MuVs, cutting the transmission route, and developing immunization strategies in China.

Key words:mumps virus;genotype G;whole genome;genetic characteristic