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目的 比较北京地区流行性腮腺炎病毒流行株和疫苗株的基因特征,初步分析疫苗效果不佳的原因.方法 通过病例免疫史分析、病毒分离鉴定、SH基因序列分析,与其他基因型参考株进行同源性比较及血凝素-神经氨酸酶(HN)基因氨基酸关键位点变异分析.结果 病毒分离阳性病例共38例,其中IgM阴性7例.在2007和2008年,病毒分离率、RT-PCR阳性率、IgM抗体阳性率都有明显下降,同时有免疫史的病例增多.实验证明无免疫史的病例病毒分离和IgM抗体阳性率更高.38株病毒均属于F基因型,疫苗株属于A基因型.SH基因流行株之间核苷酸最大差异为5.6%,与疫苗株的差异为16.0%～18.1%.部分北京株SH蛋白中保守的疏水性氨基酸发生变化,如第8位:6株L→F.各流行株之间FIN蛋白氨基酸序列最大差异为2.3%,与疫苗株差异为4.2%～5.3%.在HN上决定交叉中和能力的氨基酸位点,北京株与疫苗株存在差异,如在354位和356位,所有北京株与疫苗株都不同.北京株在HN上的N-糖基化位点也和疫苗株存在差异,如在464～466位置上为NCS,疫苗株为NCR.另有18个未知功能的氨基酸位点,所有北京株与疫苗株不同.结论 近年北京地区流行的腮腺炎病毒优势株为F基因型,未发现基因型间变异,已存在较大型内差异.北京株和疫苗株在SH和HN蛋白上都存在较大差异.

Objective To compare the genetic characteristics of mumps virus strain circulating in Beijing with vaccine strain and to preliminarily analysis the reasons of vaccine ineffectiveness. Methods The following methods were used: Isolation and identification of the mumps virus which had been circulating in Beijing, immunization history analysis, SH gene sequence analysis and comparison genotype homology with reference strains and analysis of the key amino acid sites of HN variation. Results In 38 mumps cases that virus had been isolated from, another seven cases were IgM negative. In 2007 and 2008, the positive rates on virus isolation, RT-PCR and IgMdecreased significantly, while the cases with immunization history had an increase. Cases without histories of vaccination had both higher positive rates on virus isolation and IgM. Thirty-eight strains belonged to F genotype virus, but vaccine strain was A genotype. The circulating viruses showed 5.6% sequence divergence on SH gene nucleotide and 16.0%-18.1% from vaccine strain. Conservative hydrophobic amino acids on SH protein of some Beijing strains had changed. For example, there were 6 strains, from No.8: L→F. The circulating viruses showed 2.3% sequence divergence on HN protein amino acid sequences and 4.2%-5.3% from vaccine strain. Amino acids sites, which deciding the ability of cross-neutralization of the Beijing strains and vaccine strains were different. At the 354 and 356 sites, all the Beijing strains were different from the vaccine strains. The N-glycosylation sites on HN of Beijing strains were also different from those on vaccine strains. Locations 464-466 appeared to be NCS on Beijing strain, but locations 464-466 were NCR on the vaccine strains. Another 18 unknown function amino acids sites of all Beijing strains were different from those on vaccine strains. Conclusion In recent years, genotype F became the main genotype of circulating strains in Beijing without genotype variation, but larger difference was found between them. There was a big difference between SH and HN protein of Beijing strains and vaccine strain, which might explain the ineffectiveness of the vaccine.