2004年北京婴幼儿中甲3型流感病毒血凝素基因特性对其抗原性改变的提示  

Sequence analysis of the HA1 regions of hemagglutinin gene from influenza viruses (H3N2) isolated from children in Beijing in 2004 indicated antigenic variation

作　　者：朱汝南[1] 徐红 钱渊[1] 王芳[1] 邓洁[1] 赵林清[1] 廖斌[3] 黄蓉妍[3] 

机构地区：[1]首都儿科研究所病毒室,北京市感染与免疫中心实验室,100020 [2]中国疾病预防和控制中心病毒病控制所流感室 [3]首都儿科研究所附属儿童医院内科

出　　处：《中华儿科杂志》2005年第9期653-656,共4页Chinese Journal of Pediatrics

基　　金：北京市科委新星计划(2004B34);北京市自然科学基金基础性研究实验室项目(JS96004)

摘　　要：目的了解2004年流感流行季节(2004年8月—2005年4月)北京地区婴幼儿急性呼吸道感染患儿中分离到的甲3型流感病毒是否存在抗原性的改变以及其变异程度。方法提取1株于2004年3月和32株于2004年流感流行季节从北京地区急性呼吸道感染患儿中分离到的甲3型流感病毒的病毒RNA,经RT-PCR扩增得到HA1区基因片段并进行核苷酸序列测定,使用生物信息软件分析HA1区基因序列。结果所测定的血凝素HA1区基因均为987bp,编码一个含329个氨基酸的蛋白质。将33株甲3型流感病毒流行株的血凝素(HA1)氨基酸序列与近年WHO推荐的参考疫苗株比较,我们发现一致的多处位点的氨基酸突变,而且突变位点涉及2个抗原决定簇(A、B)和受体结合部位。而2004年3月分离到的毒株在进化分析和氨基酸变异上均不同于2004年流行季节的毒株。结论对血凝素基因HA1区的序列分析结果提示2004—2005年流行季节的甲3型流感病毒较春季的流行株和2004年疫苗株出现了较大的漂移,提示其抗原性可能出现了改变。这种变异对于病毒抗原性的影响以及对于疫苗效果评价的意义值得密切关注。Objective To identify variations in hemagglutinin genes from influenza viruses （H3N2） isolated from infants and young children with acute respiratory infection （ARI） between March, 2004 and April 2005. Methods RNAs from influenza A virus strains （ subtype H3 ） isolated from specimens collected from ARI children were extracted followed by amplification for HA1 fragments from hemagglutinin （ HA ） genes by RT-PCR. The sequences of the fragments were defined by direct sequencing for the PCR products or the target inserts after the PCR fragments were cloned into the TA-cloning vector pBS-T and analyzed by bioinformatic software. Results Fragments of 987 bps of HA1 （encoding 329 amino acids） from a total of 32 strains of influenza A virus （ subtype H3 ） isolated from the 2004 season and 1 from the 2003 season were amplified and the sequences were compared with vaccine reference strains recommended by WHO which were used in recent years. There were several consistent amino acid variations which involved in both antigenic epitopes A and B and receptor binding site （RBS） for isolated strains in the 2004 influenza season compared with the vaccine strains used during the recent years and the virus strains isolated in March 2004, indicated the antigenic drift of the viruses isolated in 2004 influenza season may lead to variant viruses. Conclusion The variations of the HA genes from influenza virus （subtype H3 ） strains in the 2004-2005 influenza season were confirmed by sequence analysis for the HA1 regions of the hemagglutinin genes, which indicate that the antlgenie drift would have been caused by the diversification of the genes and the efficacy of the recently used vaccines should be keot under close watch.

关 键 词：流感病毒A型 人 血凝素 病毒性 抗原 病毒 变异(遗传学) 2004年3月 流感病毒血凝素 甲3型流感病毒 

分 类 号：R725.1[医药卫生—儿科]