输入性甲型H1N1流感病毒神经氨酸酶(NA)基因变异分析  

Analysis on neuraminidase(NA)gene variation in imported influenza A(H1N1) viruses

作　　者：黄吉城[1] 钟玉清[1] 师永霞[1] 刘丽珊[1,2] 丁国允[1] 郑夔[1] 李小波[1] 苏锦坤[1] 幸芦琴[1] 洪烨[1] 

机构地区：[1]广东出入境检验检疫局检验检疫技术中心,广东广州510700 [2]广州市黄埔区食品药品监督管理局

出　　处：《中国国境卫生检疫杂志》2014年第2期73-76,共4页Chinese Journal of Frontier Health and Quarantine

基　　金：国家质检总局科研基金项目(2012IK224;2009IK212)

摘　　要：目的分析口岸输入性甲型H1N1流感病毒神经氨酸酶(NA)基因特征及变异趋势,及早发现变异株。方法选取广东口岸入境人员中检出的64份输入性甲型H1N1流感阳性样本,对其病毒NA基因进行核苷酸序列测定。与2009年甲型H1N1流感代表株A/California/04/2009/H1N1的NA基因序列进行对比,对甲型H1N1流感病毒的NA基因进化树、核苷酸序列同源性、氨基酸序列的变异及蛋白分子结构变化等进行分析。结果 NA基因进化树分为3个分支,其中2009年、2010年病毒聚集成簇位于分支1,2011年病毒则与部分2010年检出的病毒位于较远距离的分支2和3。检出的1例病毒NA氨基酸的抗原决定簇上发生Y155H的变异,部分病毒NA蛋白在42位点上新增了一个糖基化位点,在68、386位点出现了糖基化位点的缺失。氨基酸G41R、V106I、V241I、N248D、I365T、N369K等位点的变异较为显著,但未见耐奥司他韦病毒的出现。结论甲型H1N1流感病毒NA基因已发生一定程度的变异。随着突变的不断积累,病毒极可能会通过改变其抗原性和耐药性,从而引起新的流行。Objective To analyze the characteristics and mutation tends of neuraminidase （NA） gene in imported influenza A（H1N1） viruses, and to discover variant strain early. Methods A total of 64 positive samples of influenza A（H1N1） viruses were detected from the entry cases at Guangdong ports. The nucleotide of NA gene were amplified by RT-PCR, then sequenced. Phylogenetic tree, nucleotide sequence homology, amino acid sequence homology and structural changes in proteins were analyzed by comparing with NA gene of A/California/O4/2OO9/H1N1. Results Phylogenetic tree of NA genes were divided into three lineages. Viruses detected in 2009 and 2010 were clustered together to lineages I, while all of viruses in 2011 and part in 2010 were located to the distant lineages Ⅱ and Ⅲ. NA amino acids epitopes of one case occured on Y155H variation. NA proteins of some viruses appeared to add a glycosylation sites at site 42 and miss their glycosylation sites at sites 68 and 386. Meanwhile, there were more significant amino acids variation at sites C,41R, V106I, V241I, N248D, I365T and N369K, but no Oseltamivir-resistant virus was observed. Conclusion Variations of NA in pandemic influenza A（H1N1） viruses occurred from 2009 to 2011. With the continued accumulation of mutations, the virus will likely to change its antigenic and cause a new epidemic.

关 键 词：甲型H1N1流感病毒 NA基因 变异 输入性 分析 

分 类 号：R511.7[医药卫生—内科学]