2024年上海地区H1N1流感病毒 HA 与 NA 基因的进化与变异

蒋露芳; 褚维; 乔雪飞; 孙攀; 邓森淼; 王雨茜; 赵雪; 熊家声; 吕锡宏; 董琳娟; 郑雅旭; 陈胤孜; 姜晨彦; 熊成龙; 陈健

doi:10.19428/j.cnki.sjpm.2025.250123

2024年上海地区H1N1流感病毒 HA 与 NA 基因的进化与变异

Evolution and genetic variation of HA and NA genes of H1N1 influenza virus in Shanghai， 2024

摘要

摘要:
目的分析2024年上海地区甲型H1N1流感病毒的HA和NA基因的进化与遗传变异特征，旨在理解其传播模式及其对疫苗保护效果的潜在影响。
方法收集上海地区4家医院2024年1—10月就诊流感样病例的咽拭子标本，通过实时荧光聚合酶链反应（RT⁃PCR）方法筛查并分离H1N1流感病毒。利用Illumina NovaSeq 6000平台对40株H1N1流感病毒进行全基因组测序，并对其HA和NA基因进行系统发育、遗传距离以及抗原位点的氨基酸变异分析。
结果 HA和NA基因的系统发育分析表明，2024年在上海地区流行的40株H1N1流感病毒未表现出明显的地理聚类特征，毒株来源广泛，传播链条复杂。遗传距离分析显示，40株H1N1流感病毒株的HA与NA基因组内平均遗传距离分别为0.005 1±0.000 6和0.004 6±0.000 6，接近或高于全球哨点监测株的相应数据；HA与NA变异频繁。与世界卫生组织（WHO）推荐的2023—2024年及2024—2025年北半球H1N1亚型流感疫苗株相比，上海地区40株H1N1亚型流感病毒HA蛋白的抗原变异位点发生在120、137、142、169、216、223、260、277、356、451位，其中第137位和142位在关键的抗原决定簇Ca2上；NA蛋白的抗原变异位点发生在13、50、200、257、264、339、382位。
结论 2024年上海地区H1N1流感病毒毒株的遗传背景复杂，来源多样且抗原变异，可能影响流感疫苗的保护效力。建议加强流感病毒基因组的监测与疫苗适配性评估，并针对输入性流感病毒实施更为精准的防控策略。

Abstract:
Objective To analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness.
Methods From January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes.
Results Phylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382.
Conclusion The genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

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