H9N2亚型禽流感病毒血凝素基因的分子进化分析

Molecular evolution of hemagglutinin gene of H9N2 subtype of avian influenza virus

目的揭示H9N2亚型禽流感病毒(avian influenza virus,AIV)血凝素(hemagglutinin,HA)基因氨基酸位点的变异情况并探讨其分子进化趋势。方法收集并比对EpiFlu数据库中2020年4月以前H9N2 AIV毒株HA基因序列信息,采用生物信息学的方法分析HA蛋白关键受体结合位点、裂解位点、糖基化位点的氨基酸差异。结果84.92%(4067/4809)序列HA226位点的谷氨酰胺(glutamine,Q)被亮氨酸(leucine,L)替代;来自禽类的序列发生HA-Q226 L突变的占84.75%(4013/4735),来自哺乳动物的序列发生HA-Q226 L突变的占72.97%(54/74);96.26%(4629/4809)序列HA蛋白裂解位点基序模式仍保持低致病性AIV的特点,但有180条来自禽类的序列HA蛋白裂解位点插入了2个碱性氨基酸;58.68%(2822/4809)序列新增1个或者2个潜在糖基化位点,而66.44%序列(3195/4809)丢失糖基化位点HA210-212。结论H9N2亚型AIV HA蛋白受体结合位点趋于结合人类受体,对哺乳动物的适应性增加,HA蛋白裂解位点和糖基化位点有向高致病性AIV的序列特征突变的倾向。

Objective We attempted to investigate the variation of amino acids and molecular evolution trend of hemagglutinin(HA)genes of H9N2 avian influenza virus(AIV).Methods In this study,we collected and aligned HA sequences of H9N2 AIV that submitted before April 2020 in the EpiFlu database.Then we analyzed the amino acid differences in the key sites of HA gene in bioinformatics method,including receptor binding sites,cleavage sites and glycosylation sites.Results 84.92%sequences have glutamine(Q)at the HA226 site in place of leucine(L)84.75%sequences from avian and 72.97%sequences from mammals contained such HA-Q226 L mutation.96.26%sequences still maintained the characteristics of low pathogenic AIV at the cleavage site of HA gene,except that 180 sequences from avian that two basic amino acids were inserted.Introducing one or two potential glycosylation sites were observed in 58.68%HA sequences,while loss of glycosylation site at HA210-212 in 66.44%sequences.Conclusions The key protein receptor binding sites of the HA gene of H9N2 AIV showed obvious trends to binding human receptor.It revealed H9N2 AIV′s increasing adaptation to mammals.The cleavage sites and glycoylation sites of HA protein have a mutation tendency of characteristics of highly pathogenic AIV.