Clinical Investigation | Published:

Article

RSV vs. rhinovirus bronchiolitis: difference in nasal airway microRNA profiles and NFκB signaling

Pediatric Research volume 83, pages 606614 (2018) | Download Citation

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.

Author information

Affiliations

  1. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

    • Kohei Hasegawa
    •  & Carlos A Camargo Jr
  2. Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC

    • Marcos Pérez-Losada
  3. Center for Genetic Medicine Research, Children’s National Health System, Washington, DC

    • Claire E Hoptay
    •  & Samuel Epstein
  4. Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts

    • Jonathan M Mansbach
  5. Department of Pediatrics, George Washington University School of Medicine and Health Sciences and the Division of Emergency Medicine, Children’s National Health System, Washington, DC

    • Stephen J Teach
  6. Department of Molecular Virology and Microbiology and Pediatrics, Baylor College of Medicine, Houston, Texas

    • Pedro A Piedra
  7. Division of Emergency Medicine, Children's National Health System, Washington, DC

    • Robert J Freishtat

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Competing interests

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.

Corresponding author

Correspondence to Kohei Hasegawa.

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DOI

https://doi.org/10.1038/pr.2017.309

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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The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Supplementary material is linked to the online version of the paper at http://www.nature.com/pr