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一项关于 2017-2021 年期间中国急性下呼吸道感染儿童呼吸道合胞病毒融合蛋白基因变异的多中心研究。

A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017-2021.

机构信息

Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, Beijing 100045, China.

Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China.

出版信息

Virol Sin. 2024 Oct;39(5):727-736. doi: 10.1016/j.virs.2024.09.002. Epub 2024 Sep 13.

DOI:
10.1016/j.virs.2024.09.002
PMID:39265703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11738779/
Abstract

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (ALRTI) in children under five years of age. Between 2017 and 2021, 396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China. In addition, 151 sequences from China were sourced from GenBank and GISAID, making a total of 549 RSV F gene sequences subjected to analysis. Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved, although some amino acids (AAs) have undergone changes. AA mutations with frequencies ≥ 10% were identified at six sites and the p27 region: V384I (site I), N276S (site II), R213S (site Ø), and K124N (p27) for RSV A; F45L (site I), M152I/L172Q/S173 ​L/I185V/K191R (site V), and R202Q/I206M/Q209R (site Ø) for RSV B. Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A, while the K191R, I206M, and Q209R frequencies increased by over 10% in RSV B. Notably, the nirsevimab-resistant mutation, S211N in RSV B, increased in frequency from 0% to 1.15%. Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations, with low root-mean-square deviation values. These results could provide foundational data from China for the development of RSV mAbs and vaccines.

摘要

呼吸道合胞病毒(RSV)是五岁以下儿童急性下呼吸道感染(ALRTI)的重要病因。2017 年至 2021 年,从中国九个省份的十家医院采集的 500 份 RSV 阳性咽喉拭子中获得了 396 条 RSV F 基因全长序列。此外,还从 GenBank 和 GISAID 中获取了 151 条中国序列,共计 549 条 RSV F 基因序列进行分析。系统进化和遗传多样性分析显示,2017 年至 2021 年中国流行的 RSV F 基因相对保守,但部分氨基酸(AA)发生了变化。在六个位点和 p27 区鉴定到频率≥10%的 AA 突变:RSV A 中的 V384I(位点 I)、N276S(位点 II)、R213S(位点 Ø)和 K124N(p27);RSV B 中的 F45L(位点 I)、M152I/L172Q/S173L/I185V/K191R(位点 V)和 R202Q/I206M/Q209R(位点 Ø)。比较 2020 年前后 RSV-F 的突变频率,发现 RSV A 的变化较小,而 RSV B 中的 K191R、I206M 和 Q209R 频率增加了 10%以上。值得注意的是,RSV B 中的 nirsevimab 耐药突变 S211N 频率从 0%增加到 1.15%。与各自原型的预测 RSV-F 结构对齐的代表性毒株表现出相似的构象,根均方偏差值较低。这些结果可为中国开发 RSV mAbs 和疫苗提供基础数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/5bf64f0c0122/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/924ed7d49ce3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/2ae4f17bb885/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/55c35261e180/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/020694dd9e04/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/9eb3c6429e23/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/5bf64f0c0122/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/924ed7d49ce3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/2ae4f17bb885/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/55c35261e180/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/020694dd9e04/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/9eb3c6429e23/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9df/11738779/5bf64f0c0122/figs1.jpg

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