Nasal MicroRNA Signatures for Disease Severity in Infants with Respiratory Syncytial Virus Bronchiolitis: a Multicentre Prospective Study

Overview

Journal BMJ Open Respir Res

Date 2024 Aug 1

PMID 39089741

Authors

Michihito Kyo

Zhaozhong Zhu

Ryohei Shibata

Tadao Ooka

Jonathan M Mansbach

Brennan Harmon

Andrea Hahn

Marcos Perez-Losada

Carlos A Camargo

Kohei Hasegawa

Affiliations

Soon will be listed here.

Abstract

Background: Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear.

Methods: In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA).

Results: In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, for the microtubule anchoring module, for the cell-substrate junction module.

Conclusions: In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

Citing Articles

The Molecular Basis of Asthma Exacerbations Triggered by Viral Infections: The Role of Specific miRNAs.

Kierbiedz-Guzik N, Sozanska B Int J Mol Sci. 2025; 26(1.

PMID: 39795977 PMC: 11720134. DOI: 10.3390/ijms26010120.

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