Elucidating mechanisms of interferon gamma that protect against Ebola virus infection

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Abstract Filovirus outbreaks/epidemics occur sporadically, but with increasing frequency and intensity. With no current approved filovirus therapeutics, the recent Ebola virus (EBOV) outbreaks emphasize the need for effective treatments against this highly pathogenic family of viruses. A better mechanistic understanding of effective early immune responses to EBOV will identify potential immunological approaches for controlling this infection and associated disease. Interferon gamma (IFN-γ) elicits production of antiviral proteins that control of virus replication and stimulates and activates cellular immune responses. In a series of recent studies, we demonstrated that IFN-γ profoundly inhibits EBOV infection of macrophages, an important early cellular target for the virus. We also showed that IFN-γ protects mice from EBOV challenge when mice were treated 24 hours prior to or after infection. These findings provide evidence that the immune responses elicited following IFN-γ stimulation effectively control EBOV infection and disease. Here, we will explore the contribution of both innate and cellular immunity to IFN-γ- mediated protection. In total, studies proposed here will provide critical mechanistic insights into the efficacy of this immune pathway to control filovirus infections.