Airway Secretory microRNAome Changes During Rhinovirus Infection in Early Childhood

Authors

Maria J. Gutierrez, Johns Hopkins University
Jose L. Gomez, University of Kentucky
Geovanny F. Perez, Children’s National Medical Center
Krishna Pancham, University of KentuckyFollow
Stephanie Val, Children’s National Medical Center
Dinesh K. Pillai, Children’s National Medical Center
Mamta Giri, Children’s National Medical Center
Sarah Ferrante, Children’s National Medical Center
Robert Freishtat, George Washington University
Mary C. Rose, Children’s National Medical Center
Diego Preciado, Children’s National Medical Center
Gustavo Nino, Yale University

Abstract

Background Innate 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.

Methods Nasal 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.

Results Multiscale 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.

Conclusions Comparative 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.

Document Type

Article

Publication Date

9-19-2016

Notes/Citation Information

Published in PLOS ONE, v. 11, no. 9, e0162244, p. 1-20.

© 2016 Gutierrez et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pone.0162244

Funding Information

This work was supported by grants: GN—National Heart, Lung and Blood Institute, NHLBI/HL090020 (K12 Genomics of Lung), http://www.nhlbi.nih.gov; JLG—National Heart, Lung and Blood Institute, NHLBI/1K01HL125474-01, http://www.nhlbi.nih.gov; GN—National Institute for Child Health and Human Development, NICHC/HD001399 (K12 Child Health Research Career Development Award), https://www.nichd.nih.gov; GN—National Center for Advancing Translational Sciences, KL2TR000076, https://www.nichd.nih.gov; GN—National Center for Advancing Translational Sciences, UL1TR000075, https://www.nichd.nih.gov; JLG—FAMRI: Young Clinical Scientist Award, 113393, http://www.famri.org/.

Repository Citation

Gutierrez, Maria J.; Gomez, Jose L.; Perez, Geovanny F.; Pancham, Krishna; Val, Stephanie; Pillai, Dinesh K.; Giri, Mamta; Ferrante, Sarah; Freishtat, Robert; Rose, Mary C.; Preciado, Diego; and Nino, Gustavo, "Airway Secretory microRNAome Changes During Rhinovirus Infection in Early Childhood" (2016). Pediatrics Faculty Publications. 220.
https://uknowledge.uky.edu/pediatrics_facpub/220