摘要
目的研究甲型流感病毒基因变异与生存选择压力的关系,指导保守疫苗靶位点的寻找。方法选择相同血凝素(HA)血清型具有全基因组序列的分化距离较近的多个流感病毒株系,利用Blast2程序计算各株系之间的核酸保守性、蛋白质保守性、变异核苷酸在密码子序位中的频率以及生存选择压力指数,分析与生存选择压力指数的相关性。结果HA基因较其他基因的核酸保守性为显著低;HA抗原蛋白质保守性与NS基因同为较低;HA基因受生存选择压力作用;NS、聚合酶B1(PB1)基因受选择压力较小;NA、核蛋白(NP)基因受选择压力较大;生存选择压力指数与核苷酸第3密码子位点变异频率完全相关。结论流感病毒基因变异受复制机制形成差异和生存选择压力淘汰差异双重作用影响;各基因在流感病毒生物功能中地位不同,NA、NP基因保守性较强,适宜作为疫苗靶位点候选,HA基因相比较具有一定的保守性,有望寻找到保守区段,NS、PB1基因保守性较弱,不宜作为靶位点。
Objective Study the relationship between type A influenza virus genetic variation with survival selective pressure, help for the finding of possible vaccine conserved antigen target. Methods Select seven strains of same HA （Hemagglutinin） serotype, regional and isolation time closely related type A influenza virus with full HA gene coding sequence; use Blast2 program to calcu late the parameter of nucleotide conservative, amino acid conservative, mutation ratio of codon 3rd over non 3rd locus, survival selective pressure indicator of these virus strains; analysis the parameters relationship with survival selective pressure indicator. Results Nucleotide conservative of HA gene is significantly lower than that of other genes; amino acid conservative of HA gene is similar with NS gene, all lower than that of other genes： genetic variation of HA gene is under survival selective pressure; selective pressure toward NS, PB1 gene is relatively lower than that toward NA, NP gene; survival selective pressure indicator is strongly correlated with mutation frequency upon codon 3rd locus. Conclusions Genetic variation of influenza virus is determined both by mechanism of relax replication model and survival selective pressure; genetic conservative of each gene is different, NA, NP gene could be selected as possible vaccine target for their relative high conservative, HA gene possesses me dium genetic conservative with prospective of finding more conserved epitope region within its full sequence, NS, PB1 are not recommended as vaccine candidate for their relative low genetic conservative.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2005年第4期221-224,共4页
Chinese Journal of Infectious Diseases
基金
国家自然科学基金资助项目(30200233)
