Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies

Abstract

Chronic lung disease remains the primary cause of mortality in cystic fibrosis (CF). Growing evidence suggests respiratory viral infections are often more severe in CF compared to healthy peers and contributes to pulmonary exacerbations (PEx) and deterioration of lung function. Rhinovirus is the most prevalent respiratory virus detected, particularly during exacerbations in children with CF <5 years old. However, even though rhinoviral infections are likely to be one of the factors initiating the onset of CF lung disease, there is no effective targeted treatment. A better understanding of the innate immune responses by CF airway epithelial cells, the primary site of infection for viruses, is needed to identify why viral infections are more severe in CF. The aim of this review is to present the clinical impact of virus infection in both young children and adults with CF, focusing on rhinovirus infection. Previous in vitro and in vivo investigations looking at the mechanisms behind virus infection will also be summarized. The review will finish on the potential of transcriptomics to elucidate the host-pathogen responses by CF airway cells to viral infection and identify novel therapeutic targets.

Airway Surface Liquid and Impaired Antiviral Defense in Cystic Fibrosis

“…Respiratory viral infections, including parainfluenza, respiratory syncytial virus, and influenza, are strongly associated with lung disease progression in patients with cystic fibrosis (CF) (1, 2). Human rhinovirus, the most common viral pathogen in CF, increases respiratory symptoms, airway inflammation, and the number of pulmonary exacerbations (3). Respiratory viral infections predispose patients with CF to increased prevalence of Pseudomonas aeruginosa and Staphylococcus aureus infections (4).…”