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[1999年至2012年浙江省分离的乙型流感病毒血凝素及三个内部基因的遗传变异分析]

[Analysis of genetic variation of hemagglutinin and three internal genes of influenza B virus isolated in Zhejiang province from 1999 to 2012].

作者信息

Mao Hai-yan, Sun Yi, Zhang Yan-jun, Zhou Min, Chen Yin, Li Zhen, Lu Yi-yu

机构信息

Microbiology Institute of Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2013 May;47(5):408-14.

PMID:23958122
Abstract

OBJECTIVE

To explore the characteristics of the genetic variation of hemagglutinin( HA) and three internal genes coding for the nucleoprotein ( NP) , matrix protein ( M) and nonstructural protein ( NS) of influenza B virus.

METHODS

A total of 31 strains of influenza B virus were isolated in Zhejiang province from 1999 to 2012, and then were amplified and sequenced the genes of HAl , NP, M and NS. The phylogenetic tree was constructed, the nucleotide substitution rate of the above individual gene was estimated and the variation sites of amino acids were analyzed.

RESULTS

The 31 isolated strains of influenza B virus were divided into two distinct lineages Victoria and Yamagata in the phylogenetic tree of HAl gene,represented by B/Victoria/2/87 and B/Yamagata/16/88. Phylogenetic analysis of the NP gene showed that the NP gene of Victoria-like influenza B strains which were isolated after 2010 was highly homologous with Yamagata-like isolates, and thereby they were found to be on the same branch of the phylogenetic tree of the NP gene. Nucleotide substitution rates of HAl , NP, M and NS genes were estimated to be 2. 29 x 10 -3 ,1. 39 X 10-3 ,1. 78 X 10-3 ,1. 30 X 10-3 /site per year, respectively. Variations of amino acid of HAl domain of Victoria-like isolates mainly included K48E ,L58P ,N75K,K80R,K129N/S,N165K,S172P ,Sl97N/D and A202V; while those in Yamagata-like isolates were R48K, S1501, N166Y, N203S, G230D and D233N. Determined amino acid sequences of NP of Victoria-like influenza B isolates were similar to Yamagata-like isolates after 2010 and variations happened on four characteristic amino acid sites, naming A60D, I233V, N513S and V5341, compared with previous Victoria-like influenza B isolates.

CONCLUSION

Significant variation was found among influenza B strains isolated in Zhejiang province from 1999 to 2012. The surface HAl gene evolved more rapidly than internal genes. Gene reassortment and gene mutation were the main evolutionary mechanism of influenza B virus.

摘要

目的

探讨乙型流感病毒血凝素(HA)以及编码核蛋白(NP)、基质蛋白(M)和非结构蛋白(NS)的三个内部基因的遗传变异特征。

方法

收集1999年至2012年浙江省分离的31株乙型流感病毒,对HA1、NP、M和NS基因进行扩增和测序,构建系统进化树,估计上述各基因的核苷酸替换率并分析氨基酸变异位点。

结果

在HA1基因系统进化树中,31株分离株分为两个不同的谱系,即维多利亚系和山形系,分别以B/Victoria/2/87和B/Yamagata/16/88为代表。NP基因系统进化分析显示,2010年后分离的维多利亚系乙型流感病毒NP基因与山形系毒株高度同源,在NP基因系统进化树上处于同一分支。HA1、NP、M和NS基因的核苷酸替换率分别估计为2.29×10-3、1.39×10-3、1.78×10-3、1.30×10-3/位点/年。维多利亚系分离株HA1结构域氨基酸变异主要包括K48E、L58P、N75K、K80R、K129N/S、N165K、S172P、S197N/D和A202V;山形系分离株的变异为R48K、S150I、N166Y、N203S、G230D和D233N。与以往维多利亚系乙型流感病毒分离株相比,2010年后分离的维多利亚系乙型流感病毒NP氨基酸序列与山形系相似,且在四个特征性氨基酸位点发生变异,分别为A60D、I233V、N513S和V534I。

结论

1999年至2012年浙江省分离的乙型流感病毒株间存在显著变异。表面HA1基因进化速度快于内部基因。基因重配和基因突变是乙型流感病毒的主要进化机制。

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