Azbazdar M Ekin, Dikmenogullari Mert, Kavalci Zeynep, Koçer Zeynep A
Department of Biomedicine and Health Technologies, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Türkiye.
Emerging Viral Diseases Laboratory, Izmir Biomedicine and Genome Center, Izmir, Türkiye.
Influenza Other Respir Viruses. 2025 Jul;19(7):e70134. doi: 10.1111/irv.70134.
Seasonal influenza A viruses (IAVs) remain a major global health concern, causing up to 650,000 deaths annually. Over the past century, four influenza pandemics have occurred, with H3N2 and H1N1 subtypes becoming endemic in humans. The hemagglutinin (HA) glycoprotein, essential for viral entry and a key vaccine target, contains critical antigenic sites. While antigenic drift enables immune evasion, certain substitutions can affect protein stability and intraprotein interactions, influencing viral fitness.
This study employed a Bayesian approach to investigate the phylogenetic origins of full-length HA genes from seasonal IAVs circulating in Izmir, Türkiye (2017-2023). Publicly available HA sequences from Türkiye were incorporated to assess selection pressures using four models available on Datamonkey and to examine antigenic mismatches between circulating viruses and vaccine strains. The structural impact of positively selected substitution was analyzed via molecular dynamics simulations.
Phylogenetic analysis identified four and six subclades for H1N1 and H3N2, respectively, revealing cocirculation of genetically distinct strains within the same season. Both subtypes were under negative selection, but the N260D substitution in H1N1 was consistently detected under positive selection across all models. Molecular dynamics simulations suggested that this substitution may influence intraprotein dynamics with the vestigial esterase domain, introducing a transient electrostatic bond. Furthermore, H3N2 exhibited more antigenic mismatches than H1N1, including a novel mismatch in 2022-2023.
This is the first comprehensive study documenting the genetic evolution of IAVs in Türkiye over 6 years. Regional surveillance of antigenic changes can improve vaccine strain selection and vaccination strategies.
季节性甲型流感病毒（IAV）仍然是全球主要的健康问题，每年导致多达65万人死亡。在过去的一个世纪里，发生了四次流感大流行，H3N2和H1N1亚型在人类中成为地方病。血凝素（HA）糖蛋白是病毒进入所必需的，也是关键的疫苗靶点，包含关键的抗原位点。虽然抗原漂移能够实现免疫逃逸，但某些替代可能会影响蛋白质稳定性和蛋白质内相互作用，从而影响病毒适应性。
本研究采用贝叶斯方法，调查了在土耳其伊兹密尔流行的季节性IAV全长HA基因的系统发育起源（2017 - 2023年）。纳入了土耳其公开可用的HA序列，使用Datamonkey上可用的四种模型评估选择压力，并检查流行病毒与疫苗株之间的抗原错配。通过分子动力学模拟分析了正选择替代的结构影响。
系统发育分析分别确定了H1N1和H3N2的四个和六个亚分支，揭示了同一季节内基因不同的毒株共同流行。两个亚型均处于负选择之下，但在所有模型中，H1N1中的N260D替代始终在正选择下被检测到。分子动力学模拟表明，这种替代可能会影响与残留酯酶结构域的蛋白质内动力学，引入一个瞬时静电键。此外，H3N2比H1N1表现出更多的抗原错配，包括2022 - 2023年出现的一种新的错配。
这是第一项全面记录土耳其6年期间IAV基因进化的研究。对抗原变化进行区域监测可以改善疫苗株选择和疫苗接种策略。
