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目的 基于全球GISAID数据库构建呼吸道合胞病毒(Respiratory syncytial virus,RSV)全基因组数据集，比对不同国家序列分布差异，并系统评估中美A/B型病毒的长期进化速率及关键蛋白变异规律。方法 收集2005-2024年全球RSV全基因组序列，按序列完整度与质量标准筛选后分型，分析主要国家的序列占比与亚型构成。采用BEAST软件推断中美A/B型整体及关键蛋白编码基因的进化速率，并结合线性回归与线性混合效应模型评估不同时间阶段及蛋白编码基因间的速率差异与趋势。结果 共纳入21978条序列，筛选后保留15234条(69.31%)。美国、西班牙、英国序列量最高，中国列第九。中国B型进化速率(1.2541×10-4 substitution/site/year)为A型的1.49倍；美国两型进化速率均高于中国(A、B型分别为中国的约3.38倍和3.43倍)。蛋白层面呈现一致的“G高、L低”分级模式，且仅2015-2019年蛋白间差异达到统计学显著性(P=0.033)。线性混合效应模型显示进化速率随时间显著上升(β=8.93×10-5,P<0.001)，提示全球RSV存在持续加速的演化趋势。结论 全球RSV基因组监测存在显著地区差异，中美A/B亚型进化速率及蛋白变异模式均呈结构性特征。中国B型近期演化加速的趋势可能提示正在发生的适应性演化。本研究通过整合分子钟分析与统计建模，为潜在优势株、疫苗抗原设计及多国协同监测提供了科学依据。
Abstract：Objective To construct a global whole-genome dataset of respiratory syncytial virus(RSV) based on the GISAID database, compare sequence distribution patterns across countries, and systematically evaluate long-term evolutionary rates and protein-level variation of RSV A and B subtypes in China and the United States.Methods Global RSV whole-genome sequences collected between 2005 and 2024 were retrieved from GISAID and filtered according to sequence completeness and quality criteria before subtype classification. National sequence contributions and subtype compositions were analyzed. Evolutionary rates of RSV A and B subtypes, as well as genes encoding key viral proteins, were inferred using BEAST. Linear regression and linear mixed-effects models were applied to assess differences in evolutionary rates across time periods and protein-coding genes and to evaluate overall temporal trends. Results A total of 21,978 RSV genome sequences were retrieved, of which 15,234 high-quality genomes(69.31%) were retained after filtering. The United States, Spain, and the United Kingdom contributed the largest numbers of sequences, while China ranked ninth. In China, the evolutionary rate of subtype B(1.2541 × 10-4 substitutions/site/year) was 1.49 times higher than that of subtype A. In contrast, evolutionary rates of both subtypes in the United States were substantially higher than those in China, being approximately 3.38 times higher for subtype A and 3.43 times higher for subtype B. At the protein level, a consistent hierarchical pattern was observed, with the G protein exhibiting the highest evolutionary rate and the L protein being the most conserved. Statistically significant differences among protein-coding genes were detected only during the 2015–2019 period( P = 0.033). Linear mixed-effects modeling revealed a significant temporal increase in evolutionary rates(β = 8.93×10-5, P < 0.001), indicating a sustained global acceleration of RSV evolution. Conclusion Global RSV genomic surveillance reveals pronounced geographic disparities and structured subtype-specific evolutionary patterns. The recent acceleration in the evolutionary rate of RSV subtype B in China may reflect ongoing adaptive evolution. By integrating molecular clock analysis with statistical modeling, this study provides robust quantitative evidence to support the identification of emerging dominant variants, vaccine antigen selection, and coordinated international surveillance efforts.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250384
中图分类号:R373
引用信息:
[1]曾嘉锋,曹润冬,续芮,等.全球呼吸道合胞病毒全基因组进化动力学及中美分型差异研究：基于GISAID的长期序列分析[J].病毒学报,2026,42(01):146-155.DOI:10.13242/j.cnki.bingduxuebao.250384.
基金信息:
国家重点研发计划项目（项目号：2023YFC2306000）,题目：重要病毒变异规律和预测预警研究; 传染病溯源预警与智能决策全国重点实验室腾飞计划（项目号：2024NITFID507）,题目：病毒变异自动化分析平台~~
2025-12-09
2025
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2026
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2026-01-04
2026-01-04
2026-01-04