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目的 肠道病毒A种71型（EV-A71）和柯萨奇病毒A组16型（Coxsackievirus A16, CV-A16）是手足口病和疱疹性咽峡炎等传染病的常见病原体，对儿童造成严重的疾病负担，需要对它们进行持续性地监测、风险评估和预警。方法 本研究首先采用饱和突变扫描这种生物信息学方法，评估结构蛋白上的氨基酸突变对EV-A71和CVA16的结构稳定性、受体结合力和抗体结合力的影响，然后综合这三种表型评估EV-A71和CV-A16的变异风险，最后追踪高风险位点的突变在自然序列中的流行情况。结果 通过饱和突变扫描，研究发现EV-A71和CV-A16分别有24个和25个结构稳定性的高风险位点，EV-A71有17个受体结合力的高风险位点，并确定了EV-A71的三种中和抗体和CV-A16的六种中和抗体的抗体逃逸高风险位点。综合风险评估发现了EV-A71的VP1-219等多个高风险位点，它们突变后增强了多个表型，有利于病毒生存；而另一些高风险位点如EV-A71的VP2-78等突变后会强烈抑制其他表型，不利于病毒生存。突变谱分析发现EV-A71的VP2-144和CV-A16的VP1-215等多个高风险位点已经在自然序列中具有较高突变频率，需要进一步实验验证和加强监测。结论 基于生物信息学的肠道病毒变异风险评估能够为肠道病毒的监测、风险评估和预警提供支持。
Abstract：Objective Enterovirus A71(EV-A71) and Coxsackievirus A16(CV-A16) are common pathogens associated with infectious diseases such as hand, foot, and mouth disease, and herpangina, which impose a significant disease burden on children. Continuous monitoring, risk assessment, and early warning for these viruses are therefore essential. Methods This study first employed computational saturation mutagenesis, a bioinformatics approach, to evaluate the impact of amino acid mutations in the structural proteins of EV-A71 and CV-A16 on structural stability, receptor-binding affinity, and antibody-binding affinity. Based on these three phenotypic characteristics, a comprehensive risk assessment of the variants in EV-A71 and CV-A16 was performed. Additionally, the prevalence of mutations at high-risk sites was tracked in natural sequences. Results Through computational saturation mutagenesis, 24 and 25 high-risk sites for structural stability were identified in EV-A71 and CV-A16, respectively. Additionally, 17 high-risk sites for receptor-binding affinity were found in EV-A71. High-risk sites for antibody escape were determined for three neutralizing antibodies in EV-A71 and six neutralizing antibodies in CV-A16. Comprehensive risk assessment revealed multiple high-risk sites, such as VP1-219 in EV-A71, where mutations enhanced multiple phenotypic traits, potentially benefiting viral survival. Conversely, mutations at other high-risk sites, such as VP2-78 in EV-A71, were found to strongly suppress other phenotypic traits, likely hindering viral survival. Mutation profile analysis showed that several high-risk sites, including VP2-144 in EV-A71 and VP1-215 in CV-A16, already exhibit high mutation frequencies in natural sequences, highlighting the need for further experimental validation and increased surveillance. Conclusion Bioinformatics-based risk assessment of enterovirus variants provides valuable support for the monitoring, risk evaluation, and early warning of enterovirus infections.
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基本信息:
中图分类号:R373.2
引用信息:
[1]王玲琳,童肖翔,贾永涛,等.基于生物信息学的肠道病毒A种71型和柯萨奇病毒A组16型变异风险评估[J].病毒学报().
基金信息:
宁波市公益类科技计划（项目号：2021S135）,题目：基于生物信息学的人肠道病毒基因组监测和风险评估技术研究; 宁波市自然科学基金项目（项目号：2024J314）,题目：基于饱和突变扫描和深度突变扫描的人肠道病毒基因组变异风险评估; 浙江省疾病预防控制科技计划（项目号：2026JKY233）,题目：自然、经济因素对腹泻发病率影响规律及预测模型构建研究：以浙江省某市为例
2026-03-25
2026-03-25
2026-03-25