Abstract
Background
Although rhinovirus infection is associated with increased risks of acute and chronic respiratory outcomes during childhood compared with respiratory syncytial virus (RSV), the underlying mechanisms remain unclear. We aimed to determine the differences in nasal airway microRNA profiles and their downstream effects between infants with rhinovirus and RSV bronchiolitis.
Methods
As part of a multicenter cohort study of infants hospitalized for bronchiolitis, we examined nasal samples obtained from 16 infants with rhinovirus and 16 infants with RSV. We tested nasal airway samples using microarrays to profile global microRNA expression and determine the predicted regulation of targeted transcripts. We also measured gene expression and cytokines for NFκB pathway components.
Results
Between the virus groups, 386 microRNAs were differentially expressed (false discovery rate (FDR)<0.05). In infants with rhinovirus, the NFκB pathway was highly ranked as a predicted target for these differentially expressed microRNAs compared with RSV. Pathway analysis using measured mRNA expression data validated that rhinovirus infection had upregulation of NFκB family (RelA and NFκB2) and downregulation of inhibitor κB family. Infants with rhinovirus had higher levels of NFκB-induced type-2 cytokines (IL-10 and IL-13; FDR<0.01).
Conclusion
In infants with bronchiolitis, rhinovirus and RSV infections had different nasal airway microRNA profiles associated with NFκB signaling.
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Acknowledgements
We thank Ashley Sullivan, Courtney Tierney, and Janice Espinola at the EMNet Coordinating Center (Massachusetts General Hospital, Boston, MA), and all of the site investigators and study staff for their valuable contributions to the MARC-35 study. We also thank Alkis Togias at the National Institutes of Health (Bethesda, MD) for helpful comments about the study results. Lastly, we thank the participating families for making all of this possible.
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J.M.M. has provided bronchiolitis-related consultation for Regeneron. P.A.P. received research grants from Gilead, Janssen Vaccines and Prevention, Novavax, and Regeneron, and provided bronchiolitis-related consultation for Ablynx, LFB, MedImmune, Novavax, and Regeneron. All the remaining authors declare no conflict of interest.
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STATEMENT OF FINANCIAL SUPPORT
This study was supported by the grants UG3 OD-023253, U01 AI-087881, R01 AI-114552, R01 AI-108588, R01 AI-127507, R21 HL-129909, and K12 HL-119994 from the National Institutes of Health (Bethesda, MD).
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Hasegawa, K., Pérez-Losada, M., Hoptay, C. et al. RSV vs. rhinovirus bronchiolitis: difference in nasal airway microRNA profiles and NFκB signaling. Pediatr Res 83, 606–614 (2018). https://doi.org/10.1038/pr.2017.309
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DOI: https://doi.org/10.1038/pr.2017.309
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