Interferon response and respiratory virus control are preserved in bronchial epithelial cells in asthma

Dhara A. Patel, Yingjian You, Guangming Huang, Derek E. Byers, Hyun Jik Kim, Eugene Agapov, Martin L. Moore, R. Stokes Peebles, Mario Castro, Kaharu Sumino, Adrian Shifren, Steven L. Brody, Michael J. Holtzman

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Background Some investigators find a deficiency in IFN production from airway epithelial cells infected with human rhinovirus in asthma, but whether this abnormality occurs with other respiratory viruses is uncertain. Objective To assess the effect of influenza A virus (IAV) and respiratory syncytial virus (RSV) infection on IFN production and viral level in human bronchial epithelial cells (hBECs) from subjects with and without asthma.

MethodsPrimary-culture hBECs from subjects with mild to severe asthma (n = 11) and controls without asthma (hBECs; n = 7) were infected with live or ultraviolet-inactivated IAV (WS/33 strain), RSV (Long strain), or RSV (A/2001/2-20 strain) with multiplicity of infection 0.01 to 1. Levels of virus along with IFN-β and IFN-λ and IFN-stimulated gene expression (tracked by 2′-5′-oligoadenylate synthetase 1 and myxovirus (influenza virus) resistance 1 mRNA) were determined up to 72 hours postinoculation.

Results After IAV infection, viral levels were increased 2-fold in hBECs from asthmatic subjects compared with nonasthmatic control subjects (P <.05) and this increase occurred in concert with increased IFN-λ1 levels and no significant difference in IFNB1, 2′-5′-oligoadenylate synthetase 1, or myxovirus (influenza virus) resistance 1mRNA levels. After RSV infections, viral levels were not significantly increased in hBECs from asthmatic versus nonasthmatic subjects and the only significant difference between groups was a decrease in IFN-λ levels (P <.05) that correlated with a decrease in viral titer. All these differences were found only at isolated time points and were not sustained throughout the 72-hour infection period.

Conclusions The results indicate that IAV and RSV control and IFN response to these viruses in airway epithelial cells is remarkably similar between subjects with and without asthma.

Original languageEnglish
Pages (from-to)1402-1412.e7
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number6
DOIs
StatePublished - Dec 1 2014

Keywords

  • Asthma IFN
  • influenza A virus
  • primary-culture airway epithelial cells
  • respiratory syncytial virus

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