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目的 为了揭示埃可病毒3型(Echovirus 3, E3)的分子进化特征与流行规律，完善其基因分型方法，阐明其在中国及全球的分子流行病学特征，为E3的防控策略制定提供科学依据。方法 基于本实验室收集的2003-2023年30株E3毒株，对全长VP1区进行扩增、测序，并结合GenBank中全球99条E3 VP1全长序列(45条中国序列和54条国外序列)进行系统发育分析。利用BEAST X软件估计进化速率、共同祖先时间(The most recent common ancestor, tMRCA)及有效种群大小，对代表性毒株进行全基因组测序与重组分析。结果 75株中国E3分离株与原型株Morrisey的VP1区核苷酸相似度为79.7%–82.8%。系统进化分析将全球E3划分为A–E五个基因型，其中C和D基因型可进一步划分为C1–C6和D1–D4亚型。C基因型为全球当前优势基因型，中国优势基因型与全球一致。全球E3 VP1区平均进化速率为2.95×10-3每个碱基每年，最近共同祖先追溯至1944年，中国E3分离株起源较晚(tMRCA为1981年)。全球E3经历了从A基因型到B、C、D基因型共同流行再到C基因型主要流行的更替，而中国流行的E3起源于1981年，由B基因型更替到C基因型。VP1区氨基酸突变位点分析发现不同基因型存在特异性突变位点，这为C基因型取代B基因型提供了线索。全基因组重组分析提示E3在非结构蛋白区(P2、P3)与EV-B组其他血清型存在重组。结论 本研究完善了全球E3基于全长VP1的基因分型方法，揭示了E3在中国及全球的分子流行特征，明确了其进化历程和基因型更替规律，发现了不同基因型的特异性突变位点，证实了E3存在重组现象，为其防控策略制定提供了关键依据。
Abstract：Objective To reveal the molecular evolutionary characteristics and epidemiological patterns of Echovirus 3(E3), improve its genotyping method, elucidate its molecular epidemiological features in China and globally, and provide scientific evidence for the development of E3 prevention and control strategies.Methods Based on 30 E3 strains collected in our laboratory from 2003 to 2023, the full-length VP1 region was amplified and sequenced. Combined with 99 global E3 VP1 full-length sequences from GenBank(45 Chinese sequences and 54 foreign sequences), phylogenetic analysis was performed. BEAST X software was used to estimate the evolutionary rate, time to the most recent common ancestor(tMRCA), and effective population size. Representative strains were subjected to whole-genome sequencing and recombination analysis.Results The VP1 nucleotide similarity between 75 Chinese E3 isolates and the prototype strain Morrisey ranged from 79.7% to 82.8%. Phylogenetic analysis classified global E3 into five genotypes A – E, among which genotypes C and D could be further subdivided into subtypes C1 – C6 and D1 – D4, respectively. Genotype C was the current dominant genotype globally, and the dominant genotype in China was consistent with the global pattern. The average evolutionary rate of the global E3 VP1 region was 2.95 × 10 ⁻ 3 substitutions per site per year, with the most recent common ancestor traced back to 1944. The origin of Chinese E3 isolates was later, with tMRCA of 1981. Global E3 experienced genotype replacement from genotype A to co-circulation of genotypes B, C, and D, and then to predominant circulation of genotype C. E3 circulating in China originated in 1981 and underwent replacement from genotype B to genotype C. Analysis of amino acid mutation sites in the VP1 region revealed genotype-specific mutation sites, providing clues for the replacement of genotype B by genotype C. Whole-genome recombination analysis suggested that E3 underwent recombination with other serotypes of Enterovirus B group in the non-structural protein regions(P2, P3).Conclusion This study improved the global E3 genotyping method based on full-length VP1, revealed the molecular epidemiological characteristics of E3 in China and globally, clarified its evolutionary history and genotype replacement patterns, identified genotype-specific mutation sites, confirmed recombination events in E3, and provided key evidence for the development of prevention and control strategies.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250322
中图分类号:R373.24
引用信息:
[1]朱成林,赵晓虹,周蕾,等.中国埃可病毒3型基因特征研究[J].病毒学报,2026,42(01):1-13.DOI:10.13242/j.cnki.bingduxuebao.250322.
基金信息:
国家重点研发计划（项目号：2024YFC2310403）,题目：新型肠道病毒疫苗的临床前研究~~