柯萨奇病毒 A14 的分子流行病学与进化。

Molecular Epidemiology and Evolution of Coxsackievirus A14.

机构信息

National Polio Laboratory, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosecurity, National Health Commission Key Laboratory of Medical Virology, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Henan Center for Disease Control and Prevention, Zhengzhou 450003, China.

出版信息

Viruses. 2023 Nov 26;15(12):2323. doi: 10.3390/v15122323.

DOI:10.3390/v15122323

PMID:38140564

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10748285/

Abstract

As the proportion of non-enterovirus 71 and non-coxsackievirus A16 which proportion of composition in the hand, foot, and mouth pathogenic spectrum gradually increases worldwide, the attention paid to other enteroviruses has increased. As a member of the species enterovirus A, coxsackievirus A14 (CVA14) has been epidemic around the world until now since it has been isolated. However, studies on CVA14 are poor and the effective population size, evolutionary dynamics, and recombination patterns of CVA14 are not well understood. In this study, 15 CVA14 strains were isolated from HFMD patients in mainland China from 2009 to 2019, and the complete sequences of CVA14 in GenBank as research objects were analyzed. CVA14 was divided into seven genotypes A-G based on an average nucleotide difference of the full-length VP1 coding region of more than 15%. Compared with the CVA14 prototype strain, the 15 CVA14 strains showed 84.0-84.7% nucleotide identity in the complete genome and 96.9-97.6% amino acid identity in the encoding region. Phylodynamic analysis based on 15 CVA14 strains and 22 full-length VP1 sequences in GenBank showed a mean substitution rate of 5.35 × 10 substitutions/site/year (95% HPD: 4.03-6.89 × 10) and the most recent common ancestor (tMRCA) of CVA14 dates back to 1942 (95% HPD: 1930-1950). The Bayesian skyline showed that the effective population size had experienced a decrease-increase-decrease fluctuation since 2004. The phylogeographic analysis indicated two and three possible migration paths in the world and mainland China, respectively. Four recombination patterns with others of species enterovirus A were observed in 15 CVA14 strains, among which coxsackievirus A2 (CVA2), coxsackievirus A4 (CVA4), coxsackievirus A6 (CVA6), coxsackievirus A8 (CVA8), and coxsackievirus A12 (CVA12) may act as recombinant donors in multiple regions. This study has filled the gap in the molecular epidemiological characteristics of CVA14, enriched the global CVA14 sequence database, and laid the epidemiological foundation for the future study of CVA14 worldwide.

摘要

随着手足口病病原谱中肠道病毒 71 型和柯萨奇病毒 A16 型以外的其他肠道病毒比例逐渐增加，全球对其他肠道病毒的关注度也在增加。肠道病毒 A 组柯萨奇病毒 A14 型（Coxsackievirus A14，CVA14）自分离以来，已在世界范围内流行，作为该种的一个成员，引起了人们的关注。然而，目前对 CVA14 的研究较少，其有效种群大小、进化动态和重组模式尚不清楚。本研究对中国内地 2009-2019 年手足口病患者中分离的 15 株 CVA14 进行了研究，以 GenBank 中 CVA14 全长序列为研究对象进行分析。根据全长 VP1 编码区的平均核苷酸差异大于 15%，将 CVA14 分为 7 个基因型 A-G。与 CVA14 原型株相比，15 株 CVA14 株在全基因组水平上的核苷酸同一性为 84.0%-84.7%，在编码区的氨基酸同一性为 96.9%-97.6%。基于 15 株 CVA14 株和 GenBank 中 22 条全长 VP1 序列的系统发育分析表明，CVA14 的平均替换率为 5.35×10-3 个替换/site/年（95% HPD：4.03-6.89×10-3），CVA14 的最近共同祖先（tMRCA）可追溯到 1942 年（95% HPD：1930-1950）。贝叶斯天顶图显示，自 2004 年以来，CVA14 的有效种群数量经历了减少-增加-减少的波动。系统地理分析表明，世界和中国大陆分别存在两种和三种可能的迁移路径。在 15 株 CVA14 中观察到 4 种与其他肠道病毒 A 种重组模式，其中柯萨奇病毒 A2（Coxsackievirus A2，CVA2）、柯萨奇病毒 A4（Coxsackievirus A4，CVA4）、柯萨奇病毒 A6（Coxsackievirus A6，CVA6）、柯萨奇病毒 A8（Coxsackievirus A8，CVA8）和柯萨奇病毒 A12（Coxsackievirus A12，CVA12）可能在多个地区作为重组供体。本研究填补了 CVA14 分子流行病学特征的空白，丰富了全球 CVA14 序列数据库，为未来全球 CVA14 的研究奠定了流行病学基础。