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十年间(2013 - 2023年)人类呼吸道合胞病毒的基因组进化:通向单克隆抗体监测之路的桥梁

Genomic evolution of human respiratory syncytial virus during a decade (2013-2023): bridging the path to monoclonal antibody surveillance.

作者信息

Piñana Maria, González-Sánchez Alejandra, Andrés Cristina, Vila Jorgina, Creus-Costa Anna, Prats-Méndez Ignasi, Arnedo-Muñoz Maria, Saubi Narcís, Esperalba Juliana, Rando Ariadna, Nadal-Baron Patricia, Quer Josep, González-López Juan José, Soler-Palacín Pere, Martínez-Urtaza Jaime, Larrosa Nieves, Pumarola Tomàs, Antón Andrés

机构信息

Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.

Respiratory Viruses Unit, Microbiology Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Department of Genetics and Microbiology, School of Biosciences, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

出版信息

J Infect. 2024 May;88(5):106153. doi: 10.1016/j.jinf.2024.106153. Epub 2024 Apr 6.

DOI:10.1016/j.jinf.2024.106153
PMID:38588960
Abstract

OBJECTIVES

This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023.

METHODS

Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October 2013 to May 2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes.

RESULTS

Analyzing 139,625 samples, 5.3% were HRSV-positive (3008 HRSV-A, 3882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified.

DISCUSSION

Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.

摘要

目的

本研究调查了2013年至2023年巴塞罗那地区人类呼吸道合胞病毒(HRSV)的流行情况、基因多样性和进化情况。

方法

2013年10月至2023年5月期间,从巴塞罗那瓦尔德希伯伦大学医院疑似呼吸道感染(RTI)患者中采集呼吸道标本,用于呼吸道病毒的实验室确认。对随机选择的样本采用Illumina技术进行二代测序。使用BEAST v1.10.4对全基因组序列进行系统发育分析。通过群体动态和进化分析推断选择信号和进化压力。对主要表面蛋白的突变进行基因和结构特征分析,重点关注抗原表位内的突变。

结果

分析139,625份样本,5.3%为HRSV阳性(3008份HRSV-A、3882份HRSV-B、56份HRSV-A和B混合型以及495份未分型的HRSV),在儿科人群中观察到更高的流行率。与大流行相关的季节性模式变化在2022 - 2023年恢复正常。共获得198条HRSV-A全基因组序列(占HRSV-A阳性样本的6.6%),属于GA2.3.5谱系。对于HRSV-B,对167份样本进行了测序(占HRSV-B阳性样本的4.3%),属于GB5.0.2、GB5.0.4a和GB5.0.5a。HRSV-B表现出更高的进化速率。在新冠疫情后,两种亚型最初均显示进化速率增加和有效种群大小减少,随后急剧增加。分析表明HRSV受到负选择压力。在抗原表位中鉴定出突变,包括帕利珠单抗靶向位点II中的S276N和M274I,以及尼塞韦单抗靶向位点Ø中的I206M、Q209R和S211N。

讨论

特别是在2023 - 2024季节大规模使用尼塞韦单抗的背景下,持续的流行病学和基因组监测至关重要。

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