Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000–2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014–2019, D5-CHN2: 2016–2022, and D5-EUR: 2022–2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the <i>VP1</i> region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

埃可病毒11（Echovirus 11，E11）因其与重症新生儿感染存在关联而受到广泛关注。2018年至2023年间，中国、法国及意大利均报道了与基因型D5新型变异株相关的重症新生儿病例及死亡病例激增的情况。然而，由于该病毒传播与遗传变异的背景数据不足，埃可病毒11变异株的防控工作始终受阻。因此，本研究通过收集2000-2022年中国全国急性弛缓性麻痹（acute flaccid paralysis，AFP）和手足口病（hand, foot, and mouth disease，HFMD）监测系统中的毒株，以及GenBank数据库中已发表的遗传序列，对埃可病毒11的传播动态、基因型D5的遗传变异与分子进化特征展开了研究。本研究结果揭示了埃可病毒11的传播流行规律，且基因型D5为全球范围内的优势基因型。进一步的基因型D5系统发育分析表明，该基因型可细分为三个重要的地理聚类簇：D5-CHN1（2014-2019年）、D5-CHN2（2016-2022年）以及D5-EUR（2022-2023年）。此外，研究人员在VP1区域鉴定出144个变异特异性氨基酸突变位点，以及132、262两个正选择压力位点。本研究同时鉴定出聚类簇特异性重组模式，其主要重组病毒为柯萨奇病毒B5（coxsackievirus B5，CVB5）、埃可病毒6（Echovirus 6，E6）及柯萨奇病毒B4（coxsackievirus B4，CVB4）。上述研究结果为全球埃可病毒11的传播概况提供了初步图景，并为后续埃可病毒11变异株的致病性研究提供了基础科学数据。