Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood

Abstract

BackgroundInnate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.MethodsNasal airway secretions were obtained from children (≤3 yrs. old) during PCR-confirmed RV infections (n = 10) and age-matched controls (n = 10). Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC) differentiated at air-liquid interface (ALI). Bioinformatics tools were used to determine the unified (nasal and bronchial) signature airway secretory miRNAome and changes during RV infection in children.ResultsMultiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV.ConclusionsComparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway secretion of EVs containing miR-155, which is predicted in silico to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages.

RSV‐hRV co‐infection is a risk factor for recurrent bronchial obstruction and early sensitization 3 years after bronchiolitis

“…Low blood eosinophil count on admission was a significant protective factor and high blood eosinophil count during convalescence was a significant risk factor for asthma in adulthood. Recent studies have often reported increased frequency of asthma in cases of acute bronchiolitis due to rhinoviruses . Balekian et al observed that the frequency of severe bronchiolitis and childhood asthma was similar to that in other documented reports.…”

Respiratory syncytial virus infection‐induced mucus secretion by down‐regulation of miR‐34b/c‐5p expression in airway epithelial cells

“…Intriguing, non-responsive virus-host combinations have been observed in airway secretory microRNAome in children with rhinovirus or human metapneumovirus infection. 42,43 It indicates that decreased mir-34b/c-5p expression in RSV-infected HBECs is a specific virus infection response. Notably, the down-regulation of mir-34b/c-5p have been also reported in the sputum and airway epithelia of asthma and COPD patients.…”

Airway mir-155 responses are associated with TH1 cytokine polarization in young children with viral respiratory infections

“…Studies in human infants conducted by our team [14] and others [15] have identified abundant airway production of miR-155 during naturally occurring infections caused by rhinovirus (RV) or respiratory syncytial virus (RSV). However, there is still an important unresolved paradox for the role of miR-155 during viral respiratory infections.…”