He Fenglan, Zhu Chunlong, Wu Xuan, Yi Liu, Lin Ziqi, Wen Weijie, Zhu Chunhui, Tu Junling, Qian Ke, Li Qingxiang, Ma Guangqiang, Li Hui, Wang Fang, Zhou Xianfeng
Cancer Research Center, Jiangxi University of Chinese Medicine, Nanchang, China.
Jiangxi Provincial Health Commission Key Laboratory of Pathogenic Diagnosis and Genomics of Emerging Infectious Diseases, Nanchang Center for Disease Control and Prevention, Nanchang, China.
Front Microbiol. 2024 Sep 17;15:1459917. doi: 10.3389/fmicb.2024.1459917. eCollection 2024.
In recent years, coxsackievirus (CV) A10 has been associated with increasing sporadic hand, foot, and mouth disease (HFMD) cases and outbreaks globally. In addition to mild symptoms such as pharyngitis and herpangina, CVA10-related complications or even fatality can occur. Currently, systematic phylogenetic studies of CVA10 are limited.
In this study, we first explored the epidemiological and genetic characteristics of CVA10 in Nanchang, an inland southeastern city of China, based on the HFMD surveillance network from 2015-2023.
Among 3429 enterovirus-positive cases, 110 (3.04%) were associated with CVA10, with a male-to-female ratio of 1.62. The median age of the CVA10 patients was 2.3 years (interquartile range, IQR 1.0-4.0), with 94.55% (104/110) of the patients aged less than 5 years. Phylogenetic analyses using the full-length VP1, 5'UTR, P1, P2, P3 sequences and near full-length genomes indicated that CVA10 strains ( = 57) isolated in Nanchang belonged to genogroup C; two strains identified in 2017 belonged to C1 subtypes clustered with strains from Vietnam, Madagascar, France and Spain; and the others belonged to C2 subtypes interdigitating with CVA10 isolates from mainland China, the United States and Australia. Through extensive analysis, we identified a rare F168Y mutation in epitope 4 of VP1 in a Madagascar strain of genogroup F and a Chinese strain of genogroup C. Based on Bayesian evolutionary analyses, the average nucleotide substitution rate for the VP1 gene of CV10 strains was 3.07×10 substitutions/site/year. The most recent common ancestor (tMRCA) of genogroup C was dated 1990.84, and the tMRCA of CVA10 strains from Nanchang was dated approximately 2003.16, similar to strains circulating in other regions of China, suggesting that the viruses were likely introduced and cryptically circulated in China before the establishment of the HFMD surveillance network. Recombination analysis indicated intertypic recombination of the Nanchang strain with the genogroup G strain in the 3D region.
Given the shifting dominance of viral genotypes and frequent recombination events, the existing surveillance system needs to be regulated to enhance genomic surveillance efforts on a more diverse spectrum of genotypes in the future.
近年来，柯萨奇病毒（CV）A10与全球范围内散发性手足口病（HFMD）病例及疫情的增加有关。除了咽炎和疱疹性咽峡炎等轻微症状外，CVA10相关的并发症甚至死亡也可能发生。目前，对CVA10的系统进化研究有限。
在本研究中，我们首先基于2015 - 2023年的手足口病监测网络，探索了中国东南部内陆城市南昌CVA10的流行病学和基因特征。
在3429例肠道病毒阳性病例中，110例（3.04%）与CVA10相关，男女比例为1.62。CVA10患者的中位年龄为2.3岁（四分位间距，IQR 1.0 - 4.0），94.55%（104/110）的患者年龄小于5岁。使用全长VP1、5'UTR、P1、P2、P3序列和近乎全长基因组进行的系统进化分析表明，在南昌分离的CVA10毒株（n = 57）属于C基因群；2017年鉴定的两株属于C1亚型，与来自越南、马达加斯加、法国和西班牙的毒株聚类；其他毒株属于C2亚型，与来自中国大陆、美国和澳大利亚的CVA10分离株相互交错。通过广泛分析，我们在基因群F的一株马达加斯加毒株和基因群C的一株中国毒株的VP1表位4中鉴定出一个罕见的F168Y突变。基于贝叶斯进化分析，CV10毒株VP1基因的平均核苷酸替换率为3.07×10⁻³替换/位点/年。基因群C的最近共同祖先（tMRCA）可追溯到1990.84年，南昌CVA10毒株的tMRCA约为2003.16年，与中国其他地区流行的毒株相似，这表明这些病毒可能在手足口病监测网络建立之前就已传入中国并隐匿传播。重组分析表明南昌毒株在3D区域与基因群G毒株发生了型间重组。
鉴于病毒基因型优势的变化和频繁的重组事件，未来需要规范现有的监测系统，以加强对更多样化基因型的基因组监测工作。
