Unveiling the antiviral activity of interferon epsilon in respiratory infections

Abstract

Abstract Type I interferons (IFN-I), including IFN-α and IFN-β, have demonstrated efficacy in treatments against some viral infections but with a considerable amount of undesirable side effects. IFN-ɛ, a recently discovered member of the IFN-I family, has been found to be expressed constitutively in several tissues, including the lung. However, the antiviral effect of IFN-ɛ against respiratory viral infections is largely unknown. Human respiratory syncytial virus (RSV) is the most important agent responsible for acute lower respiratory tract diseases in infants worldwide. Each year in the United States, RSV leads to approximately 2.1 million outpatient (non-hospitalization) visits among children younger than five years old, with a considerable number of hospitalizations among children younger than five years old and adults 65 years and older. Currently, no vaccine is available to prevent this respiratory tract infections, and new strategies are necessary to treat patients. Therefore, in this study, we aimed to investigate the antiviral effect of IFN-ɛ against respiratory viruses, such as RSV. Using a human epithelial cell line, we assessed the expression, susceptibility, and antiviral effect of IFN-ɛ on RSV infection. Our results demonstrate that RSV is capable of inducing IFN-ɛ. Moreover, RSV is susceptible to the antiviral activity of the rhIFN-ɛ, reducing the number of infected cells as well as the viral replication. That effect is due to the induction of the expression of ISGs with a low inflammatory profile. Overall, our findings demonstrate that RSV is susceptible to the effect of IFN-ɛ, suggesting a potential therapeutic effect of this novel member of the IFN-I family to treat respiratory viral infections. This work was funded in part by a Louisiana State University School of Veterinary Medicine Competitive Research Program Award