Abstract

Respiratory syncytial virus (RSV) is the most common respiratory virus and is associated with pediatric pneumonia, causing bronchiolitis and significant mortality in infants and young children. MicroRNAs (miRNAs) are endogenous noncoding small RNAs that function in gene regulation and are associated with host immune response and disease progression. In the present study, we profiled the global transcriptome and miRNAome of whole blood samples from children with mild or severe RSV-associated pneumonia, aiming to identify the potential biomarkers and investigate the molecular mechanisms of severe RSV-associated pediatric pneumonia. We found that expression profiles of whole blood microRNAs and mRNAs were altered and distinctly different in children with severe RSV-associated pneumonia. In particular, the four most significantly upregulated miRNAs in children with severe RSV-associated pneumonia were hsa-miR-1271-5p, hsa-miR-10a-3p, hsa-miR-125b-5p, and hsa-miR-30b-3p. The severe RSV-associated pneumonia-specific differentially expressed miRNA target interaction network was also contrasted. These target genes were further analyzed with Gene Ontology enrichment analysis. We found that most of the target genes were involved in inflammatory and immune responses, including the NF-κB signaling pathway, the MAPK signaling pathway, and T cell receptor signaling. Our findings will contribute to the identification of biomarkers and new drug design strategies to treat severe RSV-associated pediatric pneumonia.

Highlights

  • Pneumonia is a global respiratory disease that causes considerable morbidity and mortality in children

  • Respiratory syncytial virus (RSV) infection symptoms in children range from mild upper respiratory tract infection to severe respiratory infection including bronchiolitis or pneumonia, which results in hospitalization and severe complications [11, 13, 15,16,17]

  • In the comparison of whole blood miRNA profiles between children with severe RSV- and mild RSV-associated pneumonia, we identified an apparent miRNA peak at 20-24 nt (Figure 1(a))

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Summary

Introduction

Pneumonia is a global respiratory disease that causes considerable morbidity and mortality in children. It has been reported that pneumonia affects nearly 1.3 million in children annually [1, 2]. Pediatric pneumonia recurs and usually results in severe complications due to delay or incomplete treatment [3]. It is important to study the early identification of the underlying pathogenesis and effective therapeutic targets for the treatment of pediatric pneumonia. Respiratory syncytial virus (RSV) is the most common respiratory virus that is associated with pediatric pneumonia [4,5,6]. RSV infection symptoms in children range from mild upper respiratory tract infection to severe respiratory infection including bronchiolitis or pneumonia, which results in hospitalization and severe complications [11, 13, 15,16,17].

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