摘要
利用生物信息学软件和数据库研究南宁市2009~2012年度A(H3N2)亚型流感病HA基因的遗传变异规律及蛋白结构变化。通过RT-PCR扩增H3N2病毒HA基因并测序,同源比对统计毒株氨基酸位点的差异、构建系统进化树分析进化规律和同源建模分析蛋白结构的变化。系统进化树表明53株HA基因序列被分为4个类群,呈多侧支流行;所有毒株的二硫键和受体结合位点(RBS)高度保守;部分毒株HA在第45位点增加一个糖基化位点,在第144位点丢失一个糖基化位点;HA抗原决定簇氨基酸累计有30个位点发生变异,涉及5个抗原决定簇;HA晶体结构分析抗原决定簇突变位点主要发生在无规则卷曲处,大多数替换的氨基酸种类和性质相同或相似。南宁市A(H3N2)亚型流感病毒株变异活跃,2012年A(H3N2)亚型流感病毒与当年WHO推荐的疫苗株具有较远的进化距离,多数毒株具备了形成新变种的条件,是否形成新的流行株,有待深入研究。
Case study from 2009 to 2012 in Nanning on HA genetic variation rule and protein structural changes of A(H3N2) subtypes influenza virus by bioinformatics software and databases. HA gene sequences were amplified by RT-PCR and sequenced. The amino acid differences were statistically analyzed in homologous, the phylogenic tree analysis evolutionary laws was drawn, HA protein structural changes were analyzed in homology modeling with software. The phylogenetic tree showed that 53 strains of HA gene sequence were divided into four groups,which were more popular collateral branch. All the strains of disulfide bonds and receptor binding site(RBS) are highly conserved; part of strains had added a glycosylation site at amino acid position 45, while some had lost a glycosylation site at amino acid position 144. There were a total of 30 amino acids loci mutate in HA epitope,which involved five antigenic determinants. The mutations of antigenic cluster decision mainly occurred at random curl by analysis of HA crystal structure, and the type and nature of the most replacement amino acids the majority were the same or similar. The A(H3N2) subtype influenza virus strain from Nanning varied actively. There was far from evolutionary distance between the A(H3N2) in 2012 and vaccine strain recommended by WHO in Nanning. The most strains met the requirements of formatting new variants, but further research is need to do to ensure whether a new epidemic strains was formatted.
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2015年第9期1833-1841,共9页
Genomics and Applied Biology
基金
广西壮族自治区南宁市科技局科技攻关项目(200802127C)资助
