1968−2014年中国甲型H3N2流感病毒PB1基因进化分析

Evolution of PB1 genes of influenza A/H3N2 viruses in China, 1968−2014

摘要:

【目的】分析季节性H3N2流感病毒PB1基因序列的变异情况，揭示H3N2流感病毒PB1基因的分子特征与进化趋势。【方法】对1968?2014年中国地区82株人H3N2毒株、2012?2014年江苏省分离的81株甲型H3N2流感病毒、6株SIV和4株AIV H3N2亚型PB1、PB1-F2基因进行分子进化分析。【结果】1968?2014年中国H3N2流感毒株PB1核苷酸和氨基酸相似性分别为90.91%?100%和96.91%?100%。系统进化树分析，1968?2014年共173株H3N2流感病毒总体上分为4个分支，2002?2014年分离毒株位于第IV分支上，1968?1994年分离毒株位于第II和III分支；猪源H3N2亚型分布于第I、II、IV分支上；分子特征显示PB1氨基酸52、113、179、216、576、586、619、621、709位在2002年以后发生适应性改变，替换了原来的氨基酸；PB1-F2基因编码截断型蛋白长度有52、34、25、24、11 aa (猪源)，PB1-F2蛋白毒力关键位点上未出现高致病性特征突变。【结论】自1968年起H3N2亚型PB1基因变异逐步趋于稳定，且PB1-F2截断型毒株正逐渐成为一类新的进化特征，但PB1基因与其他亚型之间发生重配以及关键毒力位点的变异仍应是监测的重点。

Abstract:

[Objective] We analyzed the evolution and mutations of PB1 genes among seasonal H3N2 influenza viruses, to reveal the molecular characteristics and evolutionary trend of PB1 genes. [Methods] We analyzed PB1 and PB1-F2 genes by molecular biological software with 82 A/H3N2 viruses from 1968 to 2014 in China, 81 viruses isolated from Jiangsu Province between 2012 and 2014, 6 swine influenza viruses and 4 avian influenza viruses. [Results] PB1 segments in China showed high nucleic acid and amino acid sequence similarity (90.91% to 100%, 96.91% to 100%). The phylogenetic tree of PB1 genes was divided into 4 clusters. Strains isolated from 2002 to 2014 located in Clade IV and 1968 to 1994 were in Clade II and III. SIVs dispersed in Clade I, II, IV suggesting a reassortment of PB1genes may occurred in swine population between A/H3N2 and other subtypes. Compared to strains isolated from 1968 to 1994, the amino acid substitution of PB1 gene (52, 113, 179, 216, 576, 586, 619, 621 and 709) was observed between 2002 and 2014 with adaptive changes. Truncated PB1-F2 protein included 52, 34, 25, 24 and 11 aa (SIV). The mutation of the key virulence sites did not appear among Human A/H3N2 influenza. [Conclusion] PB1 segments of A/H3N2 influenza virus underwent stable evolution and mutation, the truncated PB1-F2 protein has become a new trend in its evolutionary process. This finding suggests that we should pay great attention on the reassortment of PB1 genes and its mutation on key virulence sites. This emphasizes the importance of virus surveillance of A/H3N2 virus.