Protective Role of Interferon Omega in Human Airway Epithelium During Human Metapneumovirus Infection 2258656

Abstract Introduction Human Metapneumovirus (HMPV) remains one of the leading causes of lower respiratory tract infections and hospitalization, particularly in infants. Currently, there is no vaccine or specific antiviral treatment for HMPV, making it crucial to explore antiviral therapy against this virus. Interferons (IFNs) are antiviral cytokines with potential clinical use. Previous work in our lab showed differential IFN responses between adult and pediatric epithelial cells after HMPV infection, where we observed that IFN-omega (IFN-ω), a type-I IFN, was the prominent IFN induced in pediatric epithelium. However, the antiviral effect of IFN-ω during HMPV infection is largely unknown. In this work, we investigated the susceptibility of HMPV infection to IFN-ω. Methods We employed a physiological 3D organotypic culture model of infection using normal human bronchial epithelial (NHBE) cells from pediatric donors, differentiated in an air-liquid interface (ALI) culture system. We used CRISPR-Cas9 and RNAi molecular techniques to investigate the mechanism of induction of IFN-ω and the mechanism by which IFN-ω exerts its antiviral effects during HMPV infection. Results Our results show that the induction of IFN-ω after HMPV infection is through a mechanism that involves the activation of Retinoic acid-inducible gene-I (RIG-I), and that IFN-ω significantly reduced HMPV infection through the induction of interferon-stimulated genes (ISGs) that block the further replication of HMPV without inducing a pro-inflammatory response. Conclusion These novel findings demonstrate the potential of IFN-ω as a modulator of epithelial antiviral responses and inflammation against HMPV infection, supporting its further evaluation as a therapeutic candidate for HMPV and other human respiratory viral infections. Funding Source Supported by the National Institute of General Medical Sciences (5P20GM130555) from the NIH, Louisiana State University, School of Veterinary Medicine Bridge Funding Grant Topic Categories Viral Immunology (VIR)