2009—2019年北京市朝阳区甲型H1N1流感病毒HA基因特征分析  

The genetic characteristics of HA gene of influenza A(H1N1)virus in Chaoyang district of Beijing in 2009—2019

作　　者：赵剑虹[1] 韩桃利 张玉松[1] 焦洋[1] 刘丹[1] 高艳[1] 房琼琼 孙灵利[1] ZHAO Jian-hong;HAN Tao-li;ZHANG Yu-song;JIAO Yang;LIU Dan;GAO Yan;FANG Qiong-qiong;SUN Ling-li(Institute of Disinfection and Pest Control,China Center for Disease Control and Prevention,Beijing 100020,China;不详)

机构地区：[1]北京市朝阳区疾病预防控制中心微生物检验科,北京100020 [2]中国疾病预防控制中心病毒与有害生物防制所,北京102206

出　　处：《中国病毒病杂志》2022年第2期126-132,共7页Chinese Journal of Viral Diseases

基　　金：2022年冬奥会突发公共卫生事件应急保障技术平台建设项目(CYSF2011);环境模拟与污染控制国家重点联合实验室(清华大学)2020年度开放课题项目(20K01ESPCT)。

摘　　要：目的分析北京市朝阳区2009—2019年甲型H1N1流感病毒(H1N1)血凝素(hemagglutinin,HA)基因特征,了解朝阳区H1N1变异情况,为评估流感疫苗有效性提供依据。方法从GenBank数据库和GISAID平台下载2009—2019年流感疫苗推荐株以及各分支主要流行株和代表株序列,与北京市朝阳区46株H1N1北京分离株的HA基因序列进行系统进化分析和氨基酸变异分析。利用MEGA 5.0软件邻接法(neighbor-joining,NJ)构建系统进化树并查看氨基酸变异位点,同时采用NetNGlyc 1.0在线软件分析HA基因潜在的糖基化位点。结果北京市朝阳区46株H1N1分离株HA基因分别属于Clade 7、Clade 8、6B、6B.1、6B.2及6C等分支。除2009年以外,2012—2019年H1N1北京市朝阳区分离株与对应年度疫苗株比较接近,同源性为90%以上。各年份H1N1北京市朝阳区分离株在4个抗原决定簇区均有氨基酸变异发生,近年H1N1北京市朝阳区分离株所在的6B.1分支序列均有S74R(Cb区)、S164T(Sa区)共同氨基酸变异;除了6B.1A2分支,其余6B.1分支序列均增加1个糖基化位点162 NQTY,其中6B.1新分支同时在162位点(Sa区)上发生氨基酸共同变异导致其糖基化位点162 NQTY转变为162 NQSY;其中,A/Beijing-Chaoyang/SWL465/2019北京市朝阳区分离株的受体结合部位发现氨基酸共同变异位点,分别位于190螺旋的D/V187A位和220环的R223Q位。结论2009—2019年北京市朝阳区H1N1分离株的HA基因不断发生变异,总体与对应年度疫苗株比较接近,但仍有抗原决定簇和受体结合部位发生氨基酸变异、糖基化位点增加,提示持续监测H1N1的HA基因的必要性,并可为流感疫苗筛选和疫情防控提供参考。Objective To describe the genetic diversity of hemagglutinin(HA)gene of influenza A(H1 N1)virus circulating in Chaoyang district of Beijing during 2009 and 2019,to understand the mutations of H1 N1 influenza viruses in the district,and to provide references for evaluating the.vaccine effectiveness.Methods The HA gene sequences of influenza vaccine recommended strains as well as the major epidemic strains and representative strains from 2009 to 2019 were downloaded from GenBank database and GISAID platform,and were compared with the HA gene sequences of 46 strains of H1 N1 isolated in Chaoyang district of Beijing to capture the systematic evolution and amino acid variation.The MEGA5 software was used to construct a phylogenetic tree and view the amino acid mutation sites,and NetNGlyc1.0 online software was used to analyze the potential glycosylation sites of the HA gene.Results Phylogenetic analysis showed that the HA genes of46 strains of H1 N1 belonged to Clade 7,Clade 8,6 B,6 B.1,6 B.2 and 6 C.Except for those in 2009.H1 N1 isolates during 2012 and 2013 were relatively close to the annual corresponding vaccine strains,with a homology of more than 90%.In addition,amino acid mutations occurred in 4 epitope regions of H1 N1 strains.In recent years,the amino acid mutations of S74 R(Cb region)and S164 T(Sa region)of H1 N1 strains in clade6 B.1 were very common.Except for those in clade 6 B.1 A2,all the other isolates in clade 6 B.1 had an extra glycosylation site 162 NQTY,which might shift to 162 NQSY with the co-mutation of amino acids at position162(Sa region)in 6 B.1 new branch.Amino acid variation sites were identified in the receptor binding site of A/Beijing-Chaoyang/SWL465/2019,which located at the D/V187 A position of the 190 helix and the R223 Q position of the 220 loop.Conclusions The HA gene of the influenza A H1 N1 virus in Chao yang district of Beijing from 2009 to 2019 keeps mutating,even though it is usually close to the corresponding annual vaccine strain,there are still amino acid mutations in antig

关 键 词：甲型H1N1流感病毒 HA基因 进化分析 氨基酸变异 

分 类 号：R373.3[医药卫生—病原生物学]