2010?2011年全球季节性H3N2流感病毒表面蛋白基因的分子遗传特性分析

Molecular genetic characteristics of surface protein genes of globe seasonal H3N2 influenza virus in 2010?2011

摘要:

【目的】分析2010年1月至2011年9月间全球季节性H3N2流感病毒血凝素 (Hemagglutinin, HA)和神经氨酸酶(Neuraminidase, NA)基因的演变和分子特征, 为流感病毒的防制提供分子信息依据。【方法】搜集期间季节性H3N2流感病毒HA和NA基因的完整核苷酸序列, 分别绘制两基因编码序列的进化树; 推导出相应的氨基酸序列, 统计不同毒株间氨基酸位点差异并分析重要功能位点的变化。【结果】在136条完整的片段4和131条片段6中, 2条HA和1条NA序列源自猪群流感病毒, 剩余的序列根据进化特征可被分为两群。相比疫苗毒株, 发生在HA和NA蛋白抗原位点的平均差异数分别为5.33和2.01个, 3个毒株分别在HA宿主受体结合位点和二硫键及NA耐药位点出现突变, 多数毒株的糖基化位点增多。江苏毒株和广东毒株分别属于群1和群2, 且两省毒株间在HA蛋白抗原位点的差异数从7到13个不等。【结论】2010年1月至2011年9月间的全球季节性H3N2病毒主要呈现两种基因进化特征。因抗原性差异对疫苗开发具有指导作用, 而多数毒株的抗原性检测信息仍然未知, 但从抗原位点和糖基化位点的变异情况来看, 多数毒株的抗原性可能已经变化, 为判断是否形成新的流行株, 应开展进一步的抗原性检测; 并且各地区卫生行政部门应根据耐药位点的变化, 制定相应的抗病毒治疗措施。

Abstract:

[Objective] The evolutionary tendency and molecular characteristics of both HA (Hemagglutinin) and NA (Neuraminidase) gene of seasonal H3N2 subtype influenza viruses isolated in 2010-2011 were to be determined, and the molecular information made an important part of control and prevention of influenza worldwide. [Methods] We collected all nucleotide sequences of segment 4 and 6 that contained complete ORF (Open Reading Frames) of HA and NA gene during Jan-2010 and Sep-2011, phylogenetic trees based on ORF sequences of two genes were constructed. Theoretical amino acid (aa) chains of every sequences were deduced to find out the variation sites referring to vaccine strain, and prevalence of changes in functional positions were analyzed. [Results] Among all 267 sequences surveyed, 3 (2 HA and 1 NA) were strains of swine origin, while others could be classified into 2 groups by evolutionary relationships. Compared with vaccine strain, average variation sites on HA and NA antigenic determinant were 5.33 and 2.01, respectively. Sites mutations on RBS (Receptor of Bonding Sites) and HA disulfide as well as NA drug resistant sites were found in 3 different isolates. N-glycosylation sites of HA and NA were increased in most isolates. Besides, variation sites on HA antigenic determinant between isolates from Jiangsu and Guangdong were accounted from 7 to 13. [Conclusion] Two kinds of gene evolutionary characteristic were found in recent seasonal H3N2 subtype viruses. Antigenic difference between epidemical strains and vaccine strain are recommended for development of new vaccines, in spite of they were still unknown, the variations on antigenic positions and N-glycosylation sites between each isolates and vaccine strain would probably alter antigenic characteristics of most isolates surveyed, so further antigen detection work is required to be carried; Health administrative departments in different districts must improve the treatment followed drug resistance situation of local epidemical strains.