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Volume 41 Issue 2
April 2026

    . doi: 10.1016/j.virs.2026.03.002
    Citation: Hongwei Zhao, Ju Yin, Yingdong Dong, Qianyu Feng, Huifang Liu, Shuaibing Han, Zhengde Xie, Lili Xu. Metatranscriptomics uncovers host immune and microbiome signatures specific to and shared between human metapneumovirus and respiratory syncytial virus infections in children .VIROLOGICA SINICA, 2026, 41(2) : 276-292.  http://dx.doi.org/10.1016/j.virs.2026.03.002
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    宏转录组学揭示儿童人偏肺病毒与呼吸道合胞病毒感染的特异性及共性宿主免疫与微生物组特征

    • 1. 首都医科大学附属北京儿童医院, 北京市儿科研究所, 呼吸道感染性疾病北京研究中心, 国家儿童医学中心, 国家呼吸系统疾病临床医学研究中心, 儿科重大疾病研究教育部重点实验室, 儿童重大传染病防治北京市重点实验室, 北京, 100045;

    • 2. 中国医学科学院, 儿童危重感染诊治创新单元(2019RU016), 北京, 100045;

    • 3. 首都医科大学附属北京儿童医院呼吸中心, 国家儿童医学中心国家呼吸系统疾病临床医学研究中心, 北京, 100045;

    • 4. 广州微远基因科技有限公司, 广州, 广东, 510300

    • 人偏肺病毒（hMPV）是一种在急性下呼吸道感染儿童中流行的呼吸道病毒，它与呼吸道合胞病毒（RSV）高度同源，RSV是儿童上呼吸道和下呼吸道感染的主要病原。虽然hMPV和RSV是肺炎病毒科中仅有的人类病原体且临床表现相似，但它们不同致病性的机制仍然知之甚少。在这项研究中，我们对2017年至2019年间收集的61名儿童（包括hMPV感染者、RSV感染者及健康对照组）的临床呼吸道样本进行了转录组学分析。分析揭示了抗病毒反应途径的共同上调，包括中性粒细胞激活和干扰素和白细胞介素介导的信号传导。相反，纤毛组织和组装途径在两种感染中普遍下调。hMPV感染独特地上调了与细胞外成分活性、离子通道复合物和神经活性配体-受体相互作用相关的途径。相反，与膜筏和膜微域相关的通路在hMPV感染患者中是唯一下调的。对差异表达的免疫相关基因和干扰素刺激基因的分析显示，EGF和FCGR1A显著增加，同时EPAS1表达降低。在hMPV感染过程中唯一上调的基因富集于细胞因子产生调节、细胞因子-细胞因子受体相互作用和PI3K/AKT信号传导，而那些唯一下调的基因涉及病毒进入和内吞囊泡途径。hMPV感染和RSV感染均显著增加了M1巨噬细胞和中性粒细胞的比例，而降低了M0和M2巨噬细胞的比例。值得注意的是，与RSV感染相比，hMPV感染导致单核细胞和活化NK细胞显著增加，同时静息记忆CD4+，T细胞减少。结果还显示，hMPV感染组唾液普氏菌的相对丰度显著高于RSV感染组，而唾液链球菌和唇炎链球菌的相对丰度显著高于RSV感染组。这些独特的免疫和微生物特征为儿童hMPV和RSV感染的发病机制提供了新的见解。

    Metatranscriptomics uncovers host immune and microbiome signatures specific to and shared between human metapneumovirus and respiratory syncytial virus infections in children

    • a. Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Research Center for Respiratory Infectious Diseases, 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, 2019RU016, Beijing 100045, China;

    • c. Department of Respiratory, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;

    • d. Vision Medical Center for Infectious Diseases, Guangzhou 510300, China

    • Human metapneumovirus (hMPV) is a prevalent respiratory virus in children with acute lower respiratory tract infections that is highly homologous with respiratory syncytial virus (RSV), the primary etiological agent of pediatric upper and lower respiratory tract infections. Although hMPV and RSV are the only human pathogens within the Pneumoviridae family and share similar clinical manifestations, the mechanisms underlying their divergent pathogenicity remain poorly understood. In this study, we performed transcriptomic analysis on clinical respiratory samples collected between 2017 and 2019 from 61 children: including hMPV-infected, RSV-infected and healthy controls. This analysis revealed a shared upregulation of antiviral response pathways, including neutrophil activation and signaling mediated by interferons and interleukins. Conversely, cilium organization and assembly pathways were commonly downregulated in both infections. hMPV infection uniquely upregulated pathways associated with extracellular component activity, ion channel complexes, and neuroactive ligand‒receptor interactions. In contrast, pathways related to membrane rafts and membrane microdomains were uniquely downregulated in hMPV-infected patients. Analysis of differentially expressed immune-related and interferon-stimulated genes revealed significant hMPV-specific increases in EGF and FCGR1A, alongside decreased EPAS1 expression. The genes that were uniquely upregulated during hMPV infection were enriched in cytokine production regulation, cytokine-cytokine receptor interactions, and PI3K/AKT signaling, whereas those that were uniquely downregulated involved the viral entry and endocytic vesicle pathways. Both hMPV infection and RSV infection significantly increased the proportions of M1 macrophages and neutrophils but decreased the proportions of M0 and M2 macrophages. Notably, hMPV infection resulted in a significant increase in monocytes and activated NK cells coupled with a decrease in resting memory CD4+ T cells, compared with RSV infection. The results also revealed a significantly greater relative abundance of Prevotella salivae in the hMPV infection group, whereas Streptococcus salivarius and Streptococcus mitis were enriched in the RSV group. These distinct immune and microbial signatures provide novel insights into the pathogenesis of pediatric hMPV and RSV infections.
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      Metatranscriptomics uncovers host immune and microbiome signatures specific to and shared between human metapneumovirus and respiratory syncytial virus infections in children

        Corresponding author: Zhengde Xie, xiezhengde@bch.com.cn
        Corresponding author: Lili Xu, justinexull26@163.com
      • a. Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Research Center for Respiratory Infectious Diseases, 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, 2019RU016, Beijing 100045, China;
      • c. Department of Respiratory, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;
      • d. Vision Medical Center for Infectious Diseases, Guangzhou 510300, China
      • Received Date: 02 July 2025
      • Accepted Date: 06 March 2026

      Abstract: Human metapneumovirus (hMPV) is a prevalent respiratory virus in children with acute lower respiratory tract infections that is highly homologous with respiratory syncytial virus (RSV), the primary etiological agent of pediatric upper and lower respiratory tract infections. Although hMPV and RSV are the only human pathogens within the Pneumoviridae family and share similar clinical manifestations, the mechanisms underlying their divergent pathogenicity remain poorly understood. In this study, we performed transcriptomic analysis on clinical respiratory samples collected between 2017 and 2019 from 61 children: including hMPV-infected, RSV-infected and healthy controls. This analysis revealed a shared upregulation of antiviral response pathways, including neutrophil activation and signaling mediated by interferons and interleukins. Conversely, cilium organization and assembly pathways were commonly downregulated in both infections. hMPV infection uniquely upregulated pathways associated with extracellular component activity, ion channel complexes, and neuroactive ligand‒receptor interactions. In contrast, pathways related to membrane rafts and membrane microdomains were uniquely downregulated in hMPV-infected patients. Analysis of differentially expressed immune-related and interferon-stimulated genes revealed significant hMPV-specific increases in EGF and FCGR1A, alongside decreased EPAS1 expression. The genes that were uniquely upregulated during hMPV infection were enriched in cytokine production regulation, cytokine-cytokine receptor interactions, and PI3K/AKT signaling, whereas those that were uniquely downregulated involved the viral entry and endocytic vesicle pathways. Both hMPV infection and RSV infection significantly increased the proportions of M1 macrophages and neutrophils but decreased the proportions of M0 and M2 macrophages. Notably, hMPV infection resulted in a significant increase in monocytes and activated NK cells coupled with a decrease in resting memory CD4+ T cells, compared with RSV infection. The results also revealed a significantly greater relative abundance of Prevotella salivae in the hMPV infection group, whereas Streptococcus salivarius and Streptococcus mitis were enriched in the RSV group. These distinct immune and microbial signatures provide novel insights into the pathogenesis of pediatric hMPV and RSV infections.

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