1999--2012年浙江省乙型流行性感冒病毒血凝素与三个内部基因的变异分析  

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

作　　者：茅海燕[1] 孙逸[1] 张严峻[1] 周敏[1] 陈寅[1] 李榛[1] 卢亦愚[1] 

机构地区：[1]浙江省疾病预防控制中心微生物所,杭州310051

出　　处：《中华预防医学杂志》2013年第5期408-414,共7页Chinese Journal of Preventive Medicine

基　　金：浙江省自然科学基金项目（Y2080987）

摘　　要：目的探讨乙型流行性感冒病毒（简称乙型流感病毒）分离株血凝素（hemagglutinin，HA）、核蛋白（nucleoprotein，NP）、基质蛋白（matrixprotein，M）和非结构蛋白（nonstructuralprotein，NS）基因的分子变异特征。方法选取浙江省1999--2012年乙型流感病毒分离代表株31株，进行HA重链区（HAl）、NP、M和NS基因测序，并构建基因进化树，估算此4个基因的核苷酸进化速率并分析其氨基酸变异位点。结果31株乙型流感病毒分离株在删J基因进化树上分别处于Victoria系和Yamagata系两大分支，分别以B／Victoria／2／87和B／Yamagata／16／88为代表。2010年之后Victoria系分离株的ⅣP基因与Yamagata系毒株高度同源，处于同一进化分支。估算HAJ、ⅣP、M和NS．基因的核苷酸年进化速率分别为2．29×10^-3、1．39×10^-3、1．78×10^-3、1．30×10^-3／位点。Victoria系分离株HAl氨基酸重要变异位点主要包括K48E、L58P、N75K、K80R、K129N／S、N165K、S172P、S197N／D和A202V，Yamagata系分离株HAl的变异位点包括R48K、S150I、N166Y、N203S、G230D和D233N。2010年之后的Victoria系分离株NP氨基酸序列与Yamagata系毒株类似，与之前的毒株存在4个特征性氨基酸位点的变异，分别为A60D、L233V、N513S和V534I。结论1999--2012年浙江省乙型流感病毒分离株发生明显变异，表面抗原基因HAl进化速度快于内部基因，基因重配和基因突变是病毒发生变异的主要机制。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 HA1 ,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 HA1 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 HA1 domain of Victoria-like isolates mainly included K48E, L58P, N75K, K80R, K129N/S, N165 K, S172P, S197N/D and A202V; while those in Yamagata-like isolates were R48K, S150I, 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 A6OD, L233V, N513S and V534I, 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 HA1 gene evolved more rapidly than internal genes. Gene reassortment and gene mutation were the main evolutionary mechanism of influenza B virus.

关 键 词：流感病毒B型 血凝素糖蛋白类 流感病毒 遗传变异 

分 类 号：R51[医药卫生—内科学]