2004年中国甲3亚型流感病毒(H3N2)抗原性及基因特性研究

目的阐明2004年中国流行的甲3亚型流感病毒血凝素抗原性及其基因变异情况。方法对2004年分离的甲3亚型毒株先进行单向血凝抑制试验及交叉血凝抑制试验;在此基础上选取不同时间、地点的甲3亚型流感毒株进行血凝素基因HA1区核苷酸序列测定并推导出其氨基酸序列,然后进行基因进化特性分析。结果单向血凝抑制实验结果表明,2004年共有52.3%毒株与A/Fujian/411/2002(H3N2)(20042005毒株)有4倍或以上的血凝抑制滴度差异,交叉血凝抑制实验结果表明,它们间的抗原比为4。HA1区核苷酸序列和氨基酸序列分析表明,我国从2004年2月分离的甲3亚型毒株开始出现了与A/Fujian/411/2002(H3N2)和A/Wellington/1/2004(H3N2)(2005年国际代表株)相比较,在其HA1蛋白分子上存在有4个氨基酸位点(159位Y>F,189位S>N,145位K>N,226位V>I)发生了替换。此类毒株首发于我国南方,然后到我国北方。结论我国2004年2月份以后所分离的甲3亚型流感毒株已经发生抗原性及基因特性的改变。

Antigenic and genetic study of hemagglutinin gene of influenza virus (H3N2) circulated in China in2004

Objective To study the antigenic and genetic characteristics of influenza (H3N2) virus circulated in China in 2004.Methods Single-way and cross-way hemagglutination inhibition (HI) tests were firstly used to determine the reactivity with the reference serum of virus isolates.Based on the serological results, virus isolates were selected according to the different time and location in China in 2004. The HA1 domain of HA gene of those virus isolates were then sequenced in order to analyze the gene characterization.Results Single-way HI test results showed that 52.3% of isolates showed 4 folds or more HI titer difference compared to A/Fujian/411/2002(H3N2)itself(international reference strain in 2004).Cross-way HI test results showed that the antigenic ratio was 4.The nucleic acid and amino acid sequence data of HA1 domain showed that the mutated virus appeared in early February of 2004, and became the dominant circulating strain gradually.There were four important mutant positions, they were 159 Y>F,189 S>N,145 K>N,226 V>I, respectively.The results also indicated that the mutated viruses originated from southern China,then transmitted to northern China, according to the analysis of time and location distribution.Conclusion The HA1 domain of HA gene of influenza virus (H3N2) isolated from 2004 in China showed mutation and antigenic drift, and the mutated viruses were becoming the dominant circulating strain in China, and showed amino acid sequence difference compared to A/Fujian/411/2002(H3N2),A/Wellington/1/2004(H3N2), the vaccine components pronounced by WHO for 2004-2005 northern hemisphere and 2005 southern hemisphere respectively, which suggested that further surveillance should be conducted to monitor the virus mutation in circulation.