Age-dependent expression and antiviral activity of interferon epsilon in respiratory epithelium.

Respiratory syncytial virus (RSV) disease burden is greatest between 6 weeks and 6 months of life, with young age the most common risk factor among hospitalized children. A robust innate immune response in the airway epithelium is crucial for mitigating RSV-associated disease, but early-life immune responses to infection remain largely unexplored. RNA-seq analysis of RSV-infected primary nasal epithelial cell cultures from healthy infants at birth and 1 year revealed diminished expression of interferon epsilon ( IMPORTANCE: Respiratory syncytial virus (RSV) is a major pediatric respiratory pathogen. Despite advances in vaccine development and monoclonal antibody prophylaxis, the immune factors driving RSV-associated disease remain unclear. Notably, severe disease is not limited to recognized high-risk groups; most affected children share only young age as a risk factor. To better understand virus-host interactions in early life, we previously derived primary airway epithelial cell cultures from the same healthy newborns at birth and at 1 year, infected them with a clinical RSV isolate, and performed total RNA sequencing. In this study, we present evidence that the transcriptional expression of interferon epsilon (