Yang Tingting, Sun Qiang, Liu Hui, Yang Ming, Chen Shuhong, Sun Wei, Xu Jun, Yan Dongmei, Zhu Shuangli, Han Zhenzhi, Xiao Jinbo, Lu Huanhuan, Liu Ying, Yang Qian, Zhang Yong
Jinan Center for Disease Control and Prevention, Jinan, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Front Microbiol. 2025 Aug 6;16:1634547. doi: 10.3389/fmicb.2025.1634547. eCollection 2025.
Hand, foot, and mouth disease (HFMD) represents a globally prevalent infectious disease that is caused by enteroviruses. Enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6) are recognized as the predominant causative agents of HFMD. CVA16 is a member of the genus within the family . B1a and B1b are the most prevalent subgenotypes, whereas the B1c subgenotype is relatively scarce. In this study, a comprehensive analysis was conducted on 15 of CVA16 B1c strains isolated from samples of patients diagnosed with HFMD in Jixi (Heilongjiang Province, China) in 2022. Subsequently, whole genome sequencing of these strains was carried out. Phylogenetic origin and potential recombination events were analyzed by aligning sequences of isolated of CVA16 B1c strains with related sequences deposited in GenBank. The CVA16 B1c isolates examined in this study exhibited a high degree of similarities. Specifically, the nucleotide similarity within the region ranged from 99.6 to 100%. The average nucleotide substitution rate of CVA16 B1c viruses worldwide was estimated to be 5.14 × 10 (4.13-6.27 × 10) substitution/site/year, and the most recent common ancestor could be traced back to 2003. The earliest CVA16 B1c strain isolated in China was traced back to 2011. Transmission pathway analysis suggested that Chinese strains may have originated in India. Recombination analysis showed that CVA16 B1c strains likely undergone recombination events with EV-A71 and CVA4. In conclusion, the analysis of a cluster of CVA16 B1c cases detected for the first time in Heilongjiang Province not only expanded the gene sequence library of CVA16 B1c strains in China but also offered an epidemiological basis for further investigations into the antigen-antibody interactions and pathogenicity of CVA16 B1c.
手足口病（HFMD）是一种由肠道病毒引起的全球流行的传染病。肠道病毒A71（EV-A71）、柯萨奇病毒A16（CVA16）和柯萨奇病毒A6（CVA6）被认为是手足口病的主要病原体。CVA16是 科 属的成员。B1a和B1b是最常见的亚型，而B1c亚型相对较少。在本研究中，对2022年从中国黑龙江省鸡西市诊断为手足口病的患者样本中分离出的15株CVA16 B1c菌株进行了全面分析。随后，对这些菌株进行了全基因组测序。通过将分离的CVA16 B1c菌株序列与GenBank中保存的相关序列进行比对，分析了系统发育起源和潜在的重组事件。本研究中检测的CVA16 B1c分离株表现出高度相似性。具体而言， 区域内的核苷酸相似性范围为99.6%至100%。全球CVA16 B1c病毒的平均核苷酸替代率估计为5.14×10（4.13 - 6.27×10）替代/位点/年，最近的共同祖先可追溯到2003年。在中国分离的最早的CVA16 B1c菌株可追溯到2011年。传播途径分析表明，中国的菌株可能起源于印度。重组分析表明，CVA16 B1c菌株可能与EV-A71和CVA4发生了重组事件。总之，对黑龙江省首次检测到的一批CVA16 B1c病例的分析不仅扩展了中国CVA16 B1c菌株的基因序列库，也为进一步研究CVA16 B1c的抗原-抗体相互作用和致病性提供了流行病学依据。
