2013-2017年中国甲型H7N9流感病毒血凝素基因进化分析

Evolution of the hemagglutinin gene of influenza A(H7N9) virus in China between 2013 and 2017

目的甲型H7N9亚型流感病毒对人具有较高致死率,了解该病毒在我国的流行态势具有重要意义。文中旨在研究2013-2017年中国地区H7N9亚型禽流感病毒血凝素(HA)基因的变异情况和进化特征。方法从全球共享禽流感数据倡议组织和美国国家生物技术中心流感病毒数据库下载2013-2017年中国地区甲型H7N9流感病毒HA基因序列,利用生物信息软件进行基因同源性分析、HA分子特征分析、系统进化分析及选择性压力分析。结果同源性分析结果显示,2013-2017年毒株的HA基因与参考毒株的同源性分别为99.0%~99.9%、98.7%~99.5%、98.4%~99.6%、76.8%~99.4%、69.9%~98.2%,同源性逐年降低。HA分子特征分析结果显示,与参考毒株相比,抗原位点发生变异的有21处,其中A区的148位、C区的285位氨基酸位点的突变频率最高;N285D的变异在2015年最高,达到23%;R148K的突变率逐年升高,在2016年和2017年分别达到65%和78.5%。系统进化分析结果显示,2013-2017年同一年份的H7N9亚型流感病毒毒株在系统进化树当中基本呈现集中分布状态;2013年大部分来自广东的毒株存在T140A的氨基酸替换。2014年毒株分布范围最广。选择性压力分析结果显示,2015年序列通过FEL和IFEL模型均得到正向选择压力位点65,2016年和2017年毒株未得到正向选择压力位点。结论甲型H7N9流感病毒逐年发生变异,且H7N9的毒株变异来源逐渐增加,加大了预防和控制的难度,应进一步加强监测,以应对病毒对宿主的不断适应和突变。

Objective Influenza A（H7N9） virus causes a relatively high mortality in humans and therefore it is of great sig-nificance to know its prevalence in China .This article aimed to study the genetic characteristics and evolution of the hemagglutinin （HA） gene of the influenza A（H7N9） virus prevailing in China between 2013 and 2017. Methods We downloaded the HA se-quences of the influenza A （ H7N9） virus prevailing in China between 2013 and 2017 from The Global Initiative on Sharing All Influen-za Data and National Center for Biotechnology Information .Using the bioinformatics software , we analyzed the homology , molecular characteristics , phyletic evolution , and selective pressure of the HA gene. Results The homology of the HA gene of the influenza A （ H7N9） virus and the reference strain was decreasing each year from 2013 to 2017, 99.0%-99.9%in 2013, 98.7%-99.5%in 2014, 98.4%-99.6%in 2015, 76.8%-99.4%in 2016, and 69.9%-98.2%in 2017.Compared with the reference strain , the HA gene of the influ-enza A（H7N9） virus underwent variations in 21 antigenic sites.The variation of N285D was the highest （23%） in 2015 and that of R148K increased yearly,reaching 65%in 2016 and 78.5% in 2017. Phylogenetic analysis showed a concentrative distribution of the influenza A （ H7N9） virus strains on the phylogenetic tree in the same year from 2013 to 2017.Amino acid substitution of T 140A was observed in most of the influenza A （ H7N9） virus strains from Guang-dong in 2013, and the widest distribution of the virus strains was found in 2014.Positive selective pressure site 65 was obtained in the sequence of 2015 using the FEL and IFEL models, but not in the strains of 2016 or 2017. Conclusion Influenza A（H7N9） virus constantly undergoes variation , which has increased the difficulty in its prevention and control .More importance should be attached to observation of the virus and response to its adaptive mutations .