广东地区甲型H3N2流行性感冒病毒毒株血凝素基因变异与进化对抗原表位的影响  

Effect of evolution and mutations of H3N2 virus hemagglutinin genes on the antigenic epitopes in Guangdong

作　　者：余靓[1] 张欣[1] 黄平[1] 梁丽君[1] 钟静[2] 曾完鍪 倪汉忠[1] 

机构地区：[1]广东省疾病预防控制中心广东省应急病原学检测重点实验室,广州511430 [2]广州市胸科医院传染科

出　　处：《中华传染病杂志》2016年第7期404-409,共6页Chinese Journal of Infectious Diseases

基　　金：广东省自然科学基金项目（2016A030313775）;广州市科技计划项目（2014J4100084）;中央财政转移支付2015年流感项目

摘　　要：目的揭示2014年至2015年广东地区流行性感冒（流感）H3N2病毒血凝素（HA）基因进化特征及抗原表位变异。方法采用时空抽样法抽样，检测2014年至2015年广东省分离的17株流感H3N2病毒HA基因核苷酸序列，下载GenBank中36株参考基因序列；比对HA基因核苷酸序列，分析基因氨基酸变异，构建遗传进化树和熵值图；同时分析2014年至2015年广东毒株HA基因的抗原表位变异和选择性。结果以疫苗株A／Texas／50／2012毒株HA基因为基准，2014年至2015年广东地区17株流感毒株HA基因共有25个位点氨基酸置换；HA1基因表位A、B、D和E发生变异，涉及11个氨基酸位点；毒株A／Guangdong／55／2015的HA基因出现N38K变异，减少1个糖基化位点。高突变位点为175位（熵值为1．16）；综合评价单似然祖先计数（SLAC）、固定效应似然比（FEL）和内部固定效应似然比（IFEL）模型筛选结果，可能正向选择位点包括位点363，负向选择位点包括位点368和425。结论广东省流感H3N2病毒HA基因表位A、B、D和E发生变异，进化正向选择位点包括位点363，负向选择位点包括位点368和425；变异累积可能导致流感H3N2病毒疫情流行。Objective To reveal evolution characteristics and antigenic epitope variabilities of hemagglutinin （HA） gene of H3N2 viruses in Guangdong during 2014-2015. Methods The HA gene nucleotide sequence of influenza H3N2 virus isolated during 2014-2015 in Guangdong Province was selected by spatial-temporal distribution. The HA gene nucleotide sequences were compared with global HA genes downloaded from GenBank and GISAID and the gene nucleotide mutations were analyzed. The phylogenetic tree and the entropy chart were conducted. Results Compared with HA gene of vaccine strain A/Texas/50/2012, the substitutions of 25 amino acid sites occurred in the HA gene of the 17 Guangdong strains during 2014 to 2015. The epitope A, B, D and E of the HA1 gene developed mutations, which involved 11 amino acid sites. One glycosylation site deletion occurred in A/Guangdong/ 55/2015 in virtue of the N38K site mutation. The high mutation site was at 175 with entropy value of 1.16. The 363 site might be the positive selection while the 368 and 425 sites might be the negative selection sites by comprehensive evaluation of the screening results of the single likelihood ancestor countincy （SLAC）, fixed effects likelihood （FEL） and internal fixed-effects likelihood （IFEL） model. Conclusions The mutations emerge in the epitopes A, B, D and E of HA gene of the Guangdong H3N2 stains. Evolution at 363 site is positive selection while those at 368 and 425 sites are negative selection.The mutation accumulation might lead to the epidemic of influenza H3N2.

关 键 词：H3N2毒株 血凝素类 突变 进化 表位 

分 类 号：R373.13[医药卫生—病原生物学]