WHO WPRO Regional Polio Reference Laboratory and National Health Commission Key Laboratory of biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
Shandong Center for Disease Control and Prevention, Jinan, Shandong, People's Republic of China.
Microbiol Spectr. 2022 Oct 26;10(5):e0195822. doi: 10.1128/spectrum.01958-22. Epub 2022 Oct 6.
Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease (HFMD) outbreaks in Asian children under 5 years of age. In severe cases, it can cause neurological complications and be life-threatening. In this study, 200 newly sequenced EV-A71 whole-genome sequences were combined with 772 EV-A71 sequences from GenBank for large-scale analysis to investigate global EV-A71 epidemiology, phylogeny, and Bayesian phylodynamic characteristics. Based on the phylogenetic analysis of the EV-A71 region, six new evolutionary lineages (lineages B, J, K, O, P, and Q) were found in this study, and the number of evolutionary lineages was expanded from 11 to 17. Temporal dynamics and recombination breakpoint analyses based on genotype C revealed that recombination of nonstructural protein-coding regions, including , is an important reason for the emergence of new lineages. The EV-A71 epidemic in the Asia-Pacific region is complex, and phylogeographic analysis found that Vietnam played a key role in the spread of subgenotypes B5 and C4. The origin of EV-A71 subgenotype C4 in China is East China, which is closely related to the prevalence of subgenotype C4 in the south and throughout China. Selection pressure analysis revealed that, in addition to VP1 amino acid residues VP1-98 and VP1-145, which are associated with EV-A71 pathogenicity, amino acid residues VP1-184 and VP1-249 were also positively selected, and their functions still need to be determined by biology and immunology. This study aimed to provide a solid theoretical basis for EV-A71-related disease surveillance and prevention, antiviral research, and vaccine development through a comprehensive analysis. EV-A71 is one of the most important pathogens causing HFMD outbreaks; however, large-scale studies of EV-A71 genomic epidemiology are currently lacking. In this study, 200 new EV-A71 whole-genome sequences were determined. Combining these with 772 EV-A71 whole-genome sequences in the GenBank database, the evolutionary and transmission characteristics of global and Asian EV-A71 were analyzed. Six new evolutionary lineages were identified in this study. We also found that recombination in nonstructural protein-coding regions, including , is an important cause for the emergence of new lineages. The results provided a solid theoretical basis for EV-A71-related disease surveillance and prevention, antiviral research, and vaccine development.
肠道病毒 A71（EV-A71）是导致亚洲 5 岁以下儿童手足口病（HFMD）爆发的主要病原体之一。在严重的情况下，它会引起神经并发症，甚至危及生命。在这项研究中，我们结合了 200 个新测序的 EV-A71 全基因组序列和来自 GenBank 的 772 个 EV-A71 序列进行大规模分析，以调查全球 EV-A71 的流行病学、系统发育和贝叶斯系统发育特征。基于 EV-A71 区的系统发育分析，本研究发现了六个新的进化谱系（谱系 B、J、K、O、P 和 Q），进化谱系的数量从 11 个扩展到 17 个。基于基因型 C 的时动态和重组断点分析表明，非结构蛋白编码区的重组，包括 ，是新谱系出现的重要原因。亚太地区的 EV-A71 流行情况复杂，系统地理分析发现越南在亚组 B5 和 C4 的传播中发挥了关键作用。中国 EV-A71 亚组 C4 的起源是华东地区，与华南和全国 C4 亚组的流行密切相关。选择压力分析表明，除了与 EV-A71 致病性相关的 VP1 氨基酸残基 VP1-98 和 VP1-145 外，VP1-184 和 VP1-249 氨基酸残基也受到正选择，其功能仍需通过生物学和免疫学来确定。本研究旨在通过综合分析为 EV-A71 相关疾病监测和预防、抗病毒研究和疫苗开发提供坚实的理论基础。EV-A71 是导致 HFMD 爆发的最重要病原体之一；然而，目前对 EV-A71 基因组流行病学的大规模研究还很缺乏。在这项研究中，我们确定了 200 个新的 EV-A71 全基因组序列。将这些序列与 GenBank 数据库中的 772 个 EV-A71 全基因组序列相结合，分析了全球和亚洲 EV-A71 的进化和传播特征。本研究发现了六个新的进化谱系。我们还发现，非结构蛋白编码区的重组，包括 ，是新谱系出现的重要原因。研究结果为 EV-A71 相关疾病监测和预防、抗病毒研究和疫苗开发提供了坚实的理论基础。
