2015-2019年湖北省甲型H1N1流感病毒流行和进化分析

Spread and evolution of influenza A(H1N1)pdm09 virus in Hubei,2015–2019

目的了解2015-2019年湖北省甲型H1N1流感病毒流行和进化特征、抗原表位和耐药位点突变情况。方法在中国流感监测信息系统下载流感病毒核酸检测阳性率并划分流行高峰,选取2015-2019年湖北省39株经实时荧光PCR检测阳性后病毒分离培养的甲型H1N1流感病毒株并测序,另在全球流感共享数据库下载13株湖北省毒株序列,采用生物信息学软件分析其进化簇分布、抗原表位和耐药突变位点,通过三维建模,分析其突变位点结构。结果 2015-2019年湖北省甲型H1N1流感病毒每年流行高峰持续长达11~14周,流行强度逐年增加,在血凝素(HA)、神经氨酸酶(NA)进化树6B簇内进化出6B.1A到6B.1A7等多个分支,发现12处HA抗原表位突变位点和2处NA基因耐药位点,其中毒力标签D222G和耐药位点I223V三维模拟结构差异明显。结论 2015-2019年甲型H1N1流感病毒流行强度不断提高,进化出多个分支簇,零星检出毒力标签和耐药突变位点,该分析有助于提高湖北省流感病毒流行病学和基因进化监测水平。

Objective To understand spread, phylogenetic characteristics, epitope and drug-resistance site of influenza A(H1N1) pdm09 virus in Hubei province during 2015–2019. Methods The spread period of the virus were divided according to the positive rate of influenza virus nucleic acid detection downloaded from influenza surveillance information system in China. Sequencing of 39 strains of influenza A(H1N1) pdm09 virus isolated from the positive samples in real-time fluorescence PCR in Hubei during 2015–2019 was conducted and 13 sequences of the strains isolated from Hubei were downloaded from global influenza database to analyze the distribution of phylogenetic clade, epitope and drug-resistant mutation sites by using bioinformatics software and simulate the structure of mutation sites by 3D modeling. Results The annual spread of influenza A(H1N1) pdm09 virus lasted for 11–14 weeks in Hubei from 2015 to 2019, and the spread intensity increased year by year. Multiple branches of 6 B.1A to 6B.1A7 evolved from 6 B clade in phylogenetic tree of the HA and NA genes. Twelve epitope substitutions of HA and two drug-resistance sites of NA were detected, and there were obvious differences in D222G substitution virulence identifying marker and drug-resistance site I223V on homology in 3D modeling structure. Conclusion The spread intensity and phylogenetic clade number of influenza A(H1N1) pdm09 virus increased In Hubei during 2015–2019. Sporadic virulence marker and drug-resistance site were detected for influenza A(H1N1) pdm09 virus. The results of this analysis can be used to improve the epidemiological research and genetic evolution surveillance of influenza virus in Hubei.