1996～2005年中国H3N2亚型人流感病毒神经氨酸酶基因特性分析

测定了1996~2005年间在中国分离并保存的395株H3N2亚型人流感病毒神经氨酸酶(NA)基因序列,应用生物信息学工具进行了分析。结果表明:NA基因序列的进化树表现为一主要进化主干伴随多侧分支进化,同一年份的毒株可以分为几个分支存在;疫苗株在NA基因序列进化树上存在明显的滞后现象;NA没有氨基酸的丢失与插入;抗原决定簇大部分位点保守且各抗原决定簇之间的变异情况各有特点,其中197~199位、431~434位和339~347位点的变异频率最高,而153位、328~336位、367~370位、400~403位抗原决定簇的氨基酸变异频率相对比较小;除了抗原决定簇外还有些氨基酸位点的变异频率很高,它们分别是18、23、30、93、143、208、216、221、249、265、267、307、385、437位氨基酸,其中143位和267位这两个位点的变异频率高于抗原决定簇位点,具体生物学意义还需要进一步研究;NA蛋白的酶活性中心位点高度保守;二硫键和糖基化位点保守。NA基因的这些特点为流感的预防、控制以及NA抑制剂药物的应用提供了一定的参考依据。

Characteristic Analysis of NA Gene of Human Influenza Viruses (H3N2) Isolated from 1996 to 2005 in China

The NA genes of 395 strains of human H3N2 influenza virus isolated from 1996 to 2005 in China were sequenced,analyzed with bioinformatics tools.The NA nucleotide sequence of phylogenetic tree showed a main evolution branch with multiple short side branches.The strains in the same year may be divided into several branches.There was an obvious lag between vaccine strains recommended by WHO and the Chinese circulating strains in phylogenetic tree of the NA nucleotide.The result also showed no animo acid deletion and insertion in the NA.In NA antigen sites,where including residues 197-199 aa,431-434 aa and 339-347aa the mutation was higher,in contrast,the residues including 153 aa,328-336 aa,367-370aa and 400-403 aa,the mutation was lower.Besides the antigenic determinant sites,there also had the other amino acid mutated highly,such as18,23,30,93,143,208,216,221,249,265,267,307,385 and 437 aa,among them 143 and 267 mutation were higher than that in antigenic determinant sites,their biological significance are not clear yet.The neuraminidase active-site residues in NA were highly conservative and the same were the disulphide bond and the glycosylation sites in NA.In conclusion,our analysis provides some information for influenza prevention and control and the NA inhibitor medicine application.