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Title:   Author  item
                                            JIANG, HAIJUN - China Agricultural Universityitem
                                            YANG, HANCHUN - China Agricultural Universityitem
                                            Kapczynski, Darrell
  Submitted to: Virology Journal
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/22/2011
                                    Publication  Date: 9/22/2011
                                    Citation: Jiang, H., Yang, H., Kapczynski, D.R. 2011. Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1 and H5N9 avian influenza viruses in lung cell cultures from different avian species. Virology Journal. 8:447. DOI 10.1186/1743-422X-8-447.Interpretive Summary: Little is known about the early immune responses of birds to avian influenza (AI) virus. Following AI infection, anti-viral proteins, including interferon, are produced rapidly by the host. The interferon protein has been shown to enhance protection against AI by decreasing the ability of the virus to replicate.  In these studies we determined the ability of chicken interferon to inhibit replication of the pandemic H1N1 AI virus, as well a H5N9 AI virus. Our results demonstrate that chicken interferon is a potent anti-viral protein, capable of reducing virus growth in chicken, duck and turkey cells. Overall, interferon was also shown to limit viral damage to cells and resulted in increased protection.
                                Technical Abstract: Type I interferons, including interferon (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 itself 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 exact role to inhibit virus replication remains unknown as does the extent to which other avian species regulate anti-viral genes. 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/SEP-4/2009) and an established avian H5N9 virus (A/turkey/Wisconsin/1968). Growth kinetics and immune response genes, including IFN-alpha, and proinflammatory cytokines (IL-1beta and IL-6), were compared over time. 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 72 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. 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.


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