长沙市2016-2023年A(H1N1)pdm09流感病毒血凝素基因进化特征  

The genetic evolution characteristics of HA gene of influenza A(H1N1)pdm09 virus in Changsha City from 2016-2023

作　　者：刘晓蕾[1] 叶文[1] 袁洁[1] 裴瑞青[1] 黄政[1] 徐明忠[1] LIU Xiaolei;YE Wen;YUAN Jie;PEI Ruiqing;HUANG Zheng;XU Mingzhong(Changsha Center For Disease Control and Prevention,Changsha,Hu'nan 410001,China)

机构地区：[1]长沙市疾病预防控制中心,湖南长沙410001

出　　处：《中国热带医学》2023年第11期1151-1156,共6页China Tropical Medicine

基　　金：湖南省自然科学基金项目(No.2023JJ60070)。

摘　　要：目的 分析2016-2023年度长沙市A(H1N1)pdm09流感病毒的血凝素(hemagglutinin, HA)基因特征,了解HA基因遗传进化趋势和氨基酸突变情况,为新形势下流感疫情的防控、流感疫苗筛选提供科学依据。方法 无特定病原(specific pathogen free, SPF)鸡胚分离法获得2016-2023年长沙市的A(H1N1)pdm09流感病毒毒株,使用Illumina公司的MiSeq对其进行二代测序测定。借助DNAStar中MegAlign软件分析HA基因的同源性,构建进化树使用Molecular Evolutionary Genetics Analysis version 11(MEGA11)软件中的Neighbor Joining(NJ)法进行。结果 2016-2023年长沙市的A(H1N1)pdm09流感病毒HA基因同源性为94.8%~99.9%,HA基因同源性逐年降低。2016-2023年度长沙市A(H1N1)pdm09分离株与WHO疫苗推荐株同源性为96.8%~99.0%,流感分离株与疫苗推荐株匹配性相对较好。长沙市的A(H1N1)pdm09流感病毒HA基因进化树显示其在6B分支中进化出多个不同分支,目前已进化到6B.1A.5a.2a分支。HA 4个抗原决定簇氨基酸位点不断发生变异,目前4个抗原决定簇中的15个抗原位点氨基酸发生突变,分离株在2023年新出现的A186T抗原变异位点近期值得关注。受体结合位点在130环相对保守,220环零星发生氨基酸变异,190环氨基酸变异位点是否日趋稳定还需加强监测。以A/California/07/2009(CY121680)为参考株,近年来长沙市大部分A(HlNl)pdm09分离株增加了162 NQTY糖基化位点,减少了276 NTTC糖基化位点,目前这2个位点的糖基化变异日趋稳定。结论 长沙市A(H1N1)pdm09病毒HA基因不断进化变异,提示病毒有逃逸免疫反应可能,我们应持续加强流感监测。Objective To analysis the genetic evolution characteristics of hemagglutinin(HA)gene of influenza A(H1N1)pdm virus in Changsha City from 2016-2023,to understand the trend of the HA genetic evolution and the mutations of the amino acid.It provides a scientific basis for the prevention and control of influenza epidemics,as well as the screening of vaccines under the new situation.Methods The A(H1N1)pdm09 virus strains from Changsha City from 2016 to 2023 were isolated using SPF chicken embryos,and then the HA genes were sequenced by MiSeq of Illumina Inc.The homology of HA gene was analyzed by MegAlign of the DNASTAR,and the phylogenetic tree was constructed using the Neighbor Joining(NJ)method in the Molecular Evolutionary Genetics Analysis version 11(MEGA11).Results The homology of the HA gene of A(H1N1)pdm virus in Changsha from 2016 to 2023 was between 94.8%-99.9%,with the HA gene homology decreasing annually.The homology between the isolated strains of A(H1N1)pdm09 in Changsha City from 2016 to 2023 and the WHO recommended vaccine strain ranged from 96.8%to 99.0%,indicating a relatively good match between the flu isolates and the recommended vaccine strain.The phylogenetic tree of the HA gene of the A(H1N1)pdm09 influenza virus in Changsha City showed that the HA gene evolved into several different branches within the 6B branch,and it had currently evolved to 6B.1A.5a.2a branch.Constant mutations had occurred at the amino acid sites of the four antigenic determinant clusters of HA protein.Currently,amino acid mutations had occurred at 15 antigenic sites within the four antigenic determinant clusters,and the newly emerged A186T antigen mutant site in the isolates from 2023 was worth recent notice.The receptor-binding sites are relatively conserved in loop 130,minor amino acid mutations occurred in loop 220,whether the amino acid mutation site in loop 190 is becoming more stable needs to be further monitored.Taking A/California/07/2009(CY121680)as the reference strain,most of the A(H1N1)pdm09 isolates in Changsh

关 键 词：A(H1N1)pdm09 HA基因 进化特征 

分 类 号：R373.1[医药卫生—病原生物学]