2019 年中国浙江一株柯萨奇病毒 A12 型的分子特征

Molecular characteristics of a coxsackievirus A12 strain in Zhejiang of China, 2019.

机构信息

Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Fosun Tower, 131 Dong An Road, Shanghai, 200032, China.

Pujiang Center for Disease Control and Prevention, Jinhua, 321000, Zhejiang, China.

出版信息

Virol J. 2022 Oct 12;19(1):160. doi: 10.1186/s12985-022-01892-1.

DOI:10.1186/s12985-022-01892-1

PMID:36224635

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9555000/

Abstract

BACKGROUND

Enterovirus A (EV-A), such as enterovirus A71 (EV-A71), generally causes hand, foot, and mouth disease (HFMD). However, limited studies focused on uncommon enterovirus serotypes such as coxsackievirus A12 (CV-A12). This study aimed to provide evidence to determine the molecular characteristics of a CV-A12 strain isolated in Zhejiang province, China.

METHODS

In routine surveillance of HFMD, we identified a child case with CV-A12 infection in 2019 in Zhejiang province, China. Enterovirus was examined by using real-time reverse transcription-PCR (qRT-PCR). A partial VP1 sequence was amplified to determine the serotype, and then a full-length CV-A12 genome was sequenced. Nucleotide and amino acid similarity was calculated with those CV-A12 strains available in GenBank. Recombination was detected using RDP 4 and SimPlot. Furthermore, phylogenetic analysis was conducted by using BEAST 1.10, and protein modeling was performed with I-TASSER webserver.

RESULTS

A full-length CV-A12 genome PJ201984 was isolated in a Chinese child with HFMD. The similarities with complete coding sequences of the CV-A12 strains in GenBank ranged between 79.3-100% (nucleotide) and 94.4-100% (amino acid), whereas it was 88.7-100.0% (nucleotide) and 97.2-100% (amino acid) when excluding the CV-A12 prototype strain Texas-12. In PJ201984, amino acid variations were more divergent in P2 and P3 regions than those in P1; the majority of those variations in VP1 (13/15) and VP4 (7/8) were similar to those documented in recently isolated CV-A12 strains in China. Furthermore, recombination was identified in P2 region, which involved a CV-A5 strain collected in China. Phylogenetic analysis revealed that PJ201984 clustered together with multiple CV-A12 strains isolated in China and the Netherlands during 2013-2018, as compared to another cluster consisting of CV-A12 strains in China and France during 2009-2015. Additionally, protein models of VP1 and VP4 in PJ201984 were well predicted to be similar to VP1 protein of EV-A71 and VP4 protein of coxsackievirus A21, respectively.

CONCLUSIONS

The full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.

摘要

背景

肠道病毒 A（EV-A），如肠道病毒 A71（EV-A71），通常会引起手足口病（HFMD）。然而，有限的研究集中在罕见的肠道病毒血清型，如柯萨奇病毒 A12（CV-A12）。本研究旨在为确定在中国浙江省分离的 CV-A12 株的分子特征提供证据。

方法

在 HFMD 的常规监测中，我们在中国浙江省 2019 年发现了一例 CV-A12 感染的儿童病例。通过实时逆转录-PCR（qRT-PCR）检测肠道病毒。扩增部分 VP1 序列以确定血清型，然后对全长 CV-A12 基因组进行测序。利用 GenBank 中可用的 CV-A12 株计算核苷酸和氨基酸相似性。使用 RDP 4 和 SimPlot 检测重组。此外，通过 BEAST 1.10 进行系统发育分析，并使用 I-TASSER webserver 进行蛋白质建模。

结果

在中国患 HFMD 的儿童中分离出全长 CV-A12 基因组 PJ201984。与 GenBank 中完整编码序列的 CV-A12 株的相似性在核苷酸水平为 79.3-100%（核苷酸）和 94.4-100%（氨基酸），而不包括 CV-A12 原型株 Texas-12 时为 88.7-100.0%（核苷酸）和 97.2-100%（氨基酸）。在 PJ201984 中，P2 和 P3 区域的氨基酸变异比 P1 区域更离散；VP1（15 个中的 13 个）和 VP4（8 个中的 7 个）中的大多数变异与中国最近分离的 CV-A12 株中的变异相似。此外，在 P2 区域发现了重组，涉及在中国收集的 CV-A5 株。系统发育分析表明，PJ201984 与 2013-2018 年期间在中国和荷兰分离的多个 CV-A12 株聚类在一起，而另一个聚类则由 2009-2015 年期间在中国和法国分离的 CV-A12 株组成。此外，PJ201984 中 VP1 和 VP4 的蛋白质模型预测与 EV-A71 的 VP1 蛋白和柯萨奇病毒 A21 的 VP4 蛋白相似。