Interferon Epsilon-Mediated Antiviral Activity Against Human Metapneumovirus and Respiratory Syncytial Virus

Interferon epsilon (IFN-ε) is a type I IFN that plays a critical role in the host immune response against pathogens. Despite having demonstrated antiviral activity in macrophages and mucosal tissues such as the female reproductive tract and the constitutive expression in mucosal tissues such as the lung, the relevance of IFN-ε against respiratory viral infections remains elusive. We present, for the first time, the expression of IFN-ε in alveolar epithelial cells and primary human bronchial epithelial cells grown in an air-liquid interface (ALI) in response to human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) infection. The molecular characterization of the IFN-ε induction by the viruses indicates that the expression of RIG-I is necessary for an optimal IFN-ε expression. Furthermore, treatment of the airway epithelial cells with rhIFN-ε induced the expression of IFN-stimulated genes (ISGs) and significantly restricted the viral replication of HMPV and RSV. These findings underscore the relevance of IFN-ε against viral infections in the respiratory tract.