Chicken interferon-induced transmembrane proteins inhibit Newcastle disease virus infection by affecting viral entry and W protein expression

Abstract Interferon-induced transmembrane proteins (IFITMs) are essential components of the innate immune system, demonstrating potent resistance to various enveloped viruses (such as influenza, West Nile, and dengue viruses) both in laboratory settings and in living organisms. Newcastle disease (ND), resulting from Newcastle disease virus (NDV), is a severe avian viral ailment with notable economic impact due to its significant mortality and morbidity rates. On the basis of the efficient antiviral effects of IFITMs, an in-depth study of the role and mechanism of NDV inhibition by chicken IFITMs (chIFITMs) is highly important for the prevention and control of this disease. In this study, we found that transient overexpression of chIFITMs effectively inhibited NDV (NDV Lasota, NDV Na) infection in DF-1 cells, with the highest inhibition rates of up to 89% and 99%, respectively, and that there was no significant difference in the antiviral effects of chIFITM1/2/3, which were not significantly different. Virus‒cell binding-entry assays revealed that chIFITMs restrict the entry process of NDV. Deleting endogenous chIFITMs enhances viral replication (more than 1.27-fold) and diminishes chIFNL3-mediated antiviral effects. Concurrently, overexpressing chIFITMs influences the expression level of the W protein; and co-immunoprecipitation experiments confirmed interaction between them. These findings suggest that the W protein could represent a novel target for the inhibition of NDV by chIFITMs. In summary, our results provide the initial comprehensive analysis of the antiviral effects of chIFITMs against NDV. This observation suggests that IFITMs are important barriers against zoonotic infections and important targets against viral invasion.