2009－2018年湖南省甲型H1N1亚型流感病毒监测结果及其全基因组进化分析

黄一伟; 张斯钰; 湛志飞; 曾舸; 黄超洋; 胡世雄; 李文超; 张红; 高立冬

doi:10.3784/j.issn.1003-9961.2019.10.006

2009－2018年湖南省甲型H1N1亚型流感病毒监测结果及其全基因组进化分析

Sentinel surveillance and whole genome evolution of influenza A (H1N1) pdm09 in Hunan, 2009–2018

摘要

摘要:
目的分析2009 — 2018年湖南省流感哨点医院甲型H1N1亚型流感监测结果，对分离病毒全基因组进化情况和分子特征进行分析。
方法在全省14个市州的23家哨点医院开展流感监测工作，每周每家哨点医院门诊采集5 ~ 20份流感样病例的咽拭子标本进行核酸检测和/或病毒分离。对分离的毒株全基因测序，使用BEAST软件贝叶斯方法构建基因进化树，序列与疫苗株进行比较。
结果2009 — 2018年湖南省流感监测哨点医院共采集流感样病例标本190 289份，其中甲型H1N1流感阳性8 014份，阳性率为4.21%。时间分布共有7个较明显的流行高峰，峰值以2009年最高。 1 ~ 5岁（占25.13%）和5 ~ 15岁（占32.83%）年龄组所占比重较多，人群男女性别比为1.23∶1。对分离的60株甲型H1N1亚型流感病毒进行同源性分析，与疫苗株相比全基因组序列的同源性在97.2% ~ 99.9%之间。贝叶斯基因进化树呈现阶梯状生长。推断最早的公共祖先出现在2 009.177年，平均进化速率为2.695×10⁻³个替换•位点⁻¹•年⁻¹。贝叶斯天际线模型分析甲型H1N1流感的种群动态2009 — 2018年间基本维持稳定。表面蛋白选择压力分析dN/dS值为0.201与0.219。表面蛋白血凝素分子的主要变异位点为L8M、S91R、S160G、S181T、A214T、I312V。 2株病毒神经氨酸酶分子出现H275Y耐药位点的突变。
结论2009 — 2018年湖南省每年甲型H1N1流感阳性率和甲型H1N1流感所占流感比例各不相同，流行高峰出现在冬季，病例以儿童和少年为主，病毒基因持续变异，种群动态稳定。

Abstract:
ObjectiveTo analyze the sentinel surveillance results of influenza A (H1N1) pdm09 and understand the whole genome evolution or molecular characteristics of the virus strains isolated in Hunan province from 2009 to 2018.
MethodsInfluenza surveillance was carried out in 23 sentinel hospitals in all 14 cities in the province. In every sentinel hospital, 5–20 throat swabs were collected from influenza-like illness (ILI) cases in outpatients every week for the nucleic acid test and/or isolation of influenza virus. The isolated strains were sequenced for whole genome, and the gene phylogenetic trees were constructed by using Bayesian method and BEAST software. The gene sequences of the strains were aligned with vaccine strain.
ResultsDuring 2009–2018, a total of 190 289 samples of ILI cases were collected in Hunan. Among them, 8 014 were positive for influenza A (H1N1) pdm09 virus (4.21%). Seven epidemics were observed, the incidence peak was in 2009. The cases mainly occurred in age group 1–5 years, accounting for 25.13% of the total, and in age group 5–15 years, accounting for 32.83%. The male to female ratio of the cases was 1.23∶1. The whole genome of 60 strains of influenza A (H1N1) pdm09 virus from Hunan during 2009–2018 was analyzed. Compared with the vaccine strain, the homology of the whole genome sequence was between 97.2% and 99.9%. The Bayesian phylogenetic tree showed a step-like growth shape. It was estimated that the earliest public ancestor appeared in 2 009.177, and the estimated average evolution rate was 2.695×10⁻³ substitutions/site/year. Bayesian skyline plot analysis showed that the population dynamics of influenza A (H1N1) pdm09 virus remained basically stable from 2009 to 2018. The surface protein selection pressure analysis showed that the values of dN/dS were 0.201 and 0.219. The main mutation sites of the hemagglutinin molecules were L8M, S91R, S160G, S181T, A214T, and I312V. Two strains had the drug resistance mutation of H275Y in neuraminidase molecule.
ConclusionDuring 2009–2018, the positive rate and proportion of influenza A (H1N1) pdm09 virus in Hunan varied with year. The incidence peak occurred in winter. The cases were mainly children and adolescents. The virus genes continued to evolve and the population dynamic was stable.

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