Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1 and H5N9 avian influenza viruses in lung cell cultures from different avian species

Background: Type I interferons, including interferon alpha (IFN-alpha), represent one of the first lines of innate immune defense against influenza virus infection. Following natural infection of chickens with avian influenza virus (AIV), transcription of IFN-alpha is quickly up regulated along with multiple other immune-related genes. Chicken IFN-alpha up regulates a number of important anti-viral response genes and has been demonstrated to be an important cytokine to establish anti-viral immunity. However, the mechanisms by which interferon inhibit virus replication in avian species remains unknown as does the biological activity of chicken interferon in other avian species. Methods: In these studies, we assessed the protective potential of exogenous chicken IFN-alpha applied to chicken, duck, and turkey primary lung cell cultures prior to infection with the pandemic H1N1 virus (A/turkey/Virginia/SEP4/2009) and an established avian H5N9 virus (A/turkey/Wisconsin/1968). Growth kinetics and induction of select immune response genes, including IFN-alpha and myxovirus-resistance gene I (Mx), as well as proinflammatory cytokines (IL-1 beta and IL-6), were measured in response to chicken IFN-alpha and viral infection over time. Results: Results demonstrate that pretreatment with chicken IFN-alpha before AIV infection significantly reduced virus replication in both chicken-and turkey-origin lung cells and to a lesser degree the duck-origin cells. Virus growth was reduced by approximately 200-fold in chicken and turkey cells and 30-fold in duck cells after 48 hours of incubation. Interferon treatment also significantly decreased the interferon and proinflammatory response during viral infection. In general, infection with the H1N1 virus resulted in an attenuated interferon and proinflammatory response in these cell lines, compared to the H5N9 virus. Conclusions: Taken together, these studies show that chicken IFN-alpha reduces virus replication, lower host innate immune response following infection, and is biologically active in other avian species.