CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection

Jennifer A. Bartlett; Eric D. Huntemann; Sateesh Krishnamurthy; Stacey M. Hartwig; Alvin Pewa; Andrew L. Thurman; Michael S. Chimenti; Eric B. Taylor; Steven M. Varga; Paul B McCray Jr

doi:10.1016/j.jcf.2025.02.003

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CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection

Journal article

Peer reviewed

CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection

Jennifer A. Bartlett, Eric D. Huntemann, Sateesh Krishnamurthy, Stacey M. Hartwig, Alvin Pewa, Andrew L. Thurman, Michael S. Chimenti, Eric B. Taylor, Steven M. Varga and Paul B McCray Jr

Journal of cystic fibrosis, Vol.24(4), pp.759-768

07/2025

DOI: 10.1016/j.jcf.2025.02.003

PMCID: PMC12767690

PMID: 39956716

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Abstract

•We compared the transcriptional responses of CF and Non-CF primary airway epithelia to respiratory syncytial virus.•RSV-infected CF epithelia had comparatively greater viral loads than Non-CF.•Induction of interferon/antiviral host defense gene expression in response to RSV infection was relatively pronounced in the CF epithelia.•RSV infection also led to downregulation of cilia genes and transient loss of cilia activity, which was prolonged in CF.•Our data suggest that delayed recovery from virus-induced cilia injury in CF epithelia may contribute to the severity of respiratory viral illness and risk of secondary bacterial infection in pwCF. In individuals with cystic fibrosis (CF), respiratory viral infections frequently result in hospitalization and have been linked to secondary bacterial infection and colonization, highlighting viral infections as possible contributors to CF lung disease progression. We hypothesized that expression of antiviral host defense genes is dysregulated in CF airway epithelia. We infected primary CF and Non-CF airway epithelia with respiratory syncytial virus (RSV) and characterized their responses at 12 hr, 24 hr, 48 hr, 72 hr, and 120 hr post infection (hpi) by RNA sequencing (RNAseq). Our analysis revealed strikingly different gene expression profiles for the CF and Non-CF epithelia over the course of the infection. While both CF and Non-CF cells exhibited an early signature for interferon signaling and antiviral defense pathways, this response was relatively exaggerated and sustained in CF epithelia. We also observed, in both genotypes, a transient downregulation of cilia-associated genes and loss of ciliary activity by 72 hpi. Interestingly, recovery of cilia activity was delayed in the CF epithelia. These findings further our understanding of innate immune dysfunction in the CF airway epithelium and suggest that virus-induced cilia injury may further compromise host defenses in CF airways.

Cystic Fibrosis

Antiviral

Cilia

Interferon

RNAseq

Viral infection

Details

Title: Subtitle: CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection
Creators: Jennifer A. Bartlett - University of Iowa
Eric D. Huntemann - University of Iowa
Sateesh Krishnamurthy - University of Iowa
Stacey M. Hartwig - University of Iowa
Alvin Pewa - University of Iowa
Andrew L. Thurman - University of Iowa
Michael S. Chimenti - University of Iowa
Eric B. Taylor - University of Iowa
Steven M. Varga - University of Iowa
Paul B McCray Jr - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Journal of cystic fibrosis, Vol.24(4), pp.759-768
DOI: 10.1016/j.jcf.2025.02.003
PMID: 39956716
PMCID: PMC12767690
NLM abbreviation: J Cyst Fibros
ISSN: 1569-1993
eISSN: 1873-5010
Publisher: Elsevier B.V
Language: English
Electronic publication date: 02/15/2025
Date published: 07/2025
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984792366202771

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