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

Yiliang Fu; Fei Li; Yun Zhu; Luci Huang; Qiuping Li; Hanwen Zhang; Lili Zhong; Hailin Zhang; Zheng-xiu Luo; Gen Lu; Jikui Deng; Lingfeng Cao; Ying Wu; Rong Jin; Lei Li; Lili Xu; Xiangpeng Chen; Zhengde Xie

doi:10.1016/j.virs.2024.09.002

October 2024

. doi: 10.1016/j.virs.2024.09.002

Citation: Yiliang Fu, Fei Li, Yun Zhu, Luci Huang, Qiuping Li, Hanwen Zhang, Lili Zhong, Hailin Zhang, Zheng-xiu Luo, Gen Lu, Jikui Deng, Lingfeng Cao, Ying Wu, Rong Jin, Lei Li, Lili Xu, Xiangpeng Chen, Zhengde Xie. 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 .VIROLOGICA SINICA, 2024, 39(5) : 727-736. http://dx.doi.org/10.1016/j.virs.2024.09.002

2017-2021年中国急性下呼吸道感染患儿呼吸道合胞病毒融合蛋白基因变异多中心研究

付艺亮 ^a,b ,
李飞 ^a,b ,
朱云 ^a,b ,
黄陆慈 ^a,b ,
李秋萍 ^a,b ,
张瀚文 ^a,b ,
钟礼立 ^c ,
张海邻 ^d ,
罗征秀 ^e ,
卢根 ^f ,
邓继岿 ^g ,
曹凌峰 ^h ,
吴滢 ⁱ ,
靳蓉 ^j ,
李磊 ^k ,
许黎黎 ^a,b ,
陈祥鹏 ^a,b,, ,
谢正德 ^a,b,,

cstr: 32224.14.j.virs.2024.09.002

a. 儿童呼吸道感染性疾病北京市重点实验室, 儿童重大疾病教育部重点实验室, 国家呼吸疾病临床研究中心, 国家儿科学重点学科(首都医科大学), 首都医科大学北京儿童医院, 国家儿童保健中心北京儿科研究所, 北京;
b. 中国医学科学院儿童危重感染研究室, 北京;
c. 湖南省人民医院, 湖南师范大学第一附属医院, 长沙;
d. 温州医科大学第二附属医院, 育英儿童医院, 儿童呼吸病科, 温州;
e. 重庆医科大学附属儿童医院, 国家儿童健康与疾病临床研究中心, 儿童发育与疾病教育部重点实验室, 重庆市儿科学重点实验室, 重庆;
f. 广州市妇女儿童医疗中心, 广州;
g. 深圳市儿童医院感染科, 深圳;
h. 复旦大学附属儿童医院检验科, 上海;
i. 上海交通大学医学院上海儿童医学中心国家儿童医学中心检验科, 上海;
j. 贵阳市妇幼保健院, 贵阳;
k. 银川市妇幼保健院, 银川

通讯作者： 陈祥鹏, chenxp1111@163.com; 谢正德, xiezhengde@bch.com.cn
收稿日期： 2024-04-18
录用日期： 2024-09-09

摘要

呼吸道合胞病毒（Respiratory Syncytial Virus, RSV）是引起5岁以下儿童急性下呼吸道感染（acute lower respiratory tract infection, ALRTI）的最重要病因之一。本研究涵盖中国2017至2021年间9个省份10家医院的500份RSV阳性咽拭子样本，通过基因扩增获得了396个RSV-F基因的完整序列；与GenBank和GISAID数据库中下载的151个中国RSV-F基因序列进行系统发育和遗传多样性分析。结果显示，2017年至2021年中国流行的RSV-F基因相对保守，但在6个中和抗原位点决定区和p27区发现了频率≥10%的AA突变：即RSV A中V384I（位点Ⅰ）、N276S（位点II）、R213S（位点Ø）和K124N（p27）；RSV B中F45L（位点I）、M152I/L172Q/S173L/I185V/K191R（位点V）和R202Q/I206M/ Q209R（位点Ø）。对比2020年前后RSV-F的突变频率，RSV A变化不大，而RSV B中K191R、I206M和Q209R的频率增加了10%以上。值得注意的是，RSV B中nirsevimab作用位点S211N的突变频率从0%增加到1.15%。A, B分离代表株与各自原型株RSV-F预测结构构象相似，均方根偏差（root-mean-square deviation， RSMD）值低。这些结果可为我国RSV单克隆抗体和疫苗的相关研发提供基础数据参考。
- 呼吸道合胞病毒
- , 急性下呼吸道感染患儿
- , F糖蛋白
- , 遗传多样性分析

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

Yiliang Fu ^a,b ,
Fei Li ^a,b ,
Yun Zhu ^a,b ,
Luci Huang ^a,b ,
Qiuping Li ^a,b ,
Hanwen Zhang ^a,b ,
Lili Zhong ^c ,
Hailin Zhang ^d ,
Zheng-xiu Luo ^e ,
Gen Lu ^f ,
Jikui Deng ^g ,
Lingfeng Cao ^h ,
Ying Wu ⁱ ,
Rong Jin ^j ,
Lei Li ^k ,
Lili Xu ^a,b ,
Xiangpeng Chen ^a,b,, ,
Zhengde Xie ^a,b,,

a. 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;
b. Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, Beijing 100045, China;
c. Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China;
d. Department of Children's Respiration Disease, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, China;
e. Department of Respiratory Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400015, China;
f. Guangzhou Women and Children's Medical Center, Guangzhou 510623, China;
g. Department of Infectious Diseases, Shenzhen Children's Hospital, Shenzhen 518026, China;
h. Department of Clinical Laboratory, Children's Hospital of Fudan University, Shanghai 201102, China;
i. Department of Clinical Laboratory Medicine, National Children's Medical Center, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China;
j. Guiyang Maternal and Child Health Hospital, Guiyang 550003, China;
k. Yinchuan Maternal and Child Health Care Hospital, Yinchuan 750001, China

Corresponding author: Xiangpeng Chen, chenxp1111@163.com Zhengde Xie, xiezhengde@bch.com.cn
Received Date: 18 April 2024
Accepted Date: 09 September 2024

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.
- Human respiratory syncytial virus (RSV)
- , Children
- , Fusion glycoprotein
- , Antigenic epitope
- , Variation

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