Age-related pharyngeal microbiome and host transcriptomic signatures underlying fever responses in RSV bronchiolitis

Ying Li; Jingyuan Zhang; Haizhou Liu; Muhammad Noman; Muhammad Arif Rizwan; Ismaila Damilare Isiaka; Hebin Chen; Wenqing Li; Nan Zhao; Yan Li; Yamin Sun; Xiaoxia Lu; Di Liu; Yi Yan

doi:10.1016/j.virs.2026.05.002

June 2026

. doi: 10.1016/j.virs.2026.05.002

Citation: Ying Li, Jingyuan Zhang, Haizhou Liu, Muhammad Noman, Muhammad Arif Rizwan, Ismaila Damilare Isiaka, Hebin Chen, Wenqing Li, Nan Zhao, Yan Li, Yamin Sun, Xiaoxia Lu, Di Liu, Yi Yan. Age-related pharyngeal microbiome and host transcriptomic signatures underlying fever responses in RSV bronchiolitis .VIROLOGICA SINICA, 2026, 41(3) : 574-585. http://dx.doi.org/10.1016/j.virs.2026.05.002

RSV毛细支气管炎发热反应相关的年龄依赖性咽部微生物组与宿主转录组特征

李颖 ^a,b,c,d ,
张敬媛 ^c,d ,
刘海舟 ^a ,
Muhammad Noman ^a,b ,
Muhammad Arif Rizwan ^a,b ,
Ismaila Damilare Isiaka ^a,b ,
陈和斌 ^c,d ,
李文清 ^c,d ,
赵南 ^c,d ,
李岩 ^c,d,e ,
孙亚民 ^f ,
陆小霞 ^c,d,, ,
刘翟 ^a,b,, ,
闫艺 ^c,d,,

a. 中国科学院武汉病毒研究所病毒与生物安全全国重点实验室;
b. 中国科学院大学;
c. 华中科技大学同济医学院武汉儿童医院呼吸内科;
d. 华中科技大学同济医学院武汉儿童医院妇儿健康研究所儿童呼吸疾病研究室;
e. 华中科技大学同济医学院基础医学部病原生物学系及同济医学院人畜共患传染病重症诊治国家重点实验室;
f. 首都医科大学北京地坛医院传染病溯源预警与智能决策全国重点实验室

通讯作者： 陆小霞, lusi74@163.com; 刘翟, liud@wh.iov.cn; 闫艺, yanyi_1996@163.com
收稿日期： 2026-01-07
录用日期： 2026-05-12

摘要

呼吸道合胞病毒（Respiratory syncytial virus，RSV）是婴幼儿毛细支气管炎及住院的重要病原体，其临床表现具有明显年龄依赖性，其中发热发生率随患儿年龄增长逐渐升高，但其生物学基础尚不明确。本研究基于RSV毛细支气管炎住院婴幼儿前瞻性队列，结合临床特征、咽部微生物组、宿主转录组及宿主-微生物互作网络进行年龄分层分析。临床数据显示，发热发生率随年龄增长呈明显上升趋势。年龄和发热是解释微生物组和宿主基因表达差异的主要因素；发热相关微生物组变化幅度有限但存在高度年龄依赖，不存在跨婴幼儿期一致的微生物特征；而宿主转录组则呈现明显的发育阶段差异，从早期宿主防御相关程序的相对减弱到后期抗病毒及炎症效应激活，并伴随免疫调控重塑。综上所述，RSV毛细支气管炎中的发热并不代表统一的炎症反应，而是不同年龄阶段程序化免疫状态的体现，提示临床上RSV毛细支气管炎应结合年龄对发热进行分层解读。
- 呼吸道合胞病毒
- , 毛细支气管炎
- , 年龄依赖性
- , 发热
- , 宿主反应
- , 气道微生物组

Age-related pharyngeal microbiome and host transcriptomic signatures underlying fever responses in RSV bronchiolitis

Ying Li ^a,b,c,d ,
Jingyuan Zhang ^c,d ,
Haizhou Liu ^a ,
Muhammad Noman ^a,b ,
Muhammad Arif Rizwan ^a,b ,
Ismaila Damilare Isiaka ^a,b ,
Hebin Chen ^c,d ,
Wenqing Li ^c,d ,
Nan Zhao ^c,d ,
Yan Li ^c,d,e ,
Yamin Sun ^f ,
Xiaoxia Lu ^c,d,, ,
Di Liu ^a,b,, ,
Yi Yan ^c,d,,

a. State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
b. University of Chinese Academy of Sciences, Beijing 101409, China;
c. Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China;
d. Pediatric Respiratory Disease Laboratory, Institute of Maternal and Child Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China;
e. Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
f. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 101409, China

Corresponding author: Xiaoxia Lu, lusi74@163.com Di Liu, liud@wh.iov.cn Yi Yan, yanyi_1996@163.com
Received Date: 07 January 2026
Accepted Date: 12 May 2026

Abstract

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infancy and exhibits pronounced age-dependent clinical heterogeneity. Fever becomes increasingly prevalent with age, yet whether febrile representation reflects a uniform inflammatory and immune phenotype across infancy remains unclear. In this prospective cohort of infants hospitalized with RSV bronchiolitis, we performed an integrated analysis of clinical features, pharyngeal microbiome composition, host transcriptomic profiles, and host-microbe interaction networks, with particular attention to age-related variation in fever-associated patterns. Clinically, fever prevalence exhibited a strong age-dependent increase across infancy. Correspondingly, canonical correspondence analysis identified age and fever as dominant gradients related to variation in both pharyngeal microbiome composition and host gene expression. Although no significant age-dependent correlations were observed at the global microbial and host transcriptomic levels in the fever-age interaction model, distinct patterns of microbial and host responses related to fever were observed across different age groups. Specifically, ranked gene set enrichment analysis indicated that febrile infants in early infancy showed relative attenuation of host defense-related programs, whereas older infants showed stronger enrichment of antiviral and inflammatory effector pathways, with more selective regulatory and signaling-associated patterns in late infancy. Integrated host-microbe network analysis further delineated a coherent developmental trajectory of fever-associated interaction architectures, evolving from densely interconnected regulatory networks in early infancy to modular, selectively coupled, host-centered configurations with advancing age. Together, febrile responses in RSV bronchiolitis should not be interpreted as a uniform biological phenotype across infancy and support age-aware interpretation of fever in pediatric RSV infection.
- Respiratory syncytial virus (RSV)
- , Bronchiolitis
- , Age-dependent
- , Fever
- , Host response
- , Airway microbiome

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