Interferon-? Inhibits Ebola Virus Infection

Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.; Monick, Martha M.; Maury, Wendy

Based on the promising results we observed with IFNγ protection of EBOV GP/rVSV infected mice, we next sought to determine the ability of IFNγ to protect mice from lethal challenge with mouse-adapted EBOV (MA-EBOV). BALB/c mice were administered 3 or 10 μg of IFNγ i.p. and challenged i.p. with MA-EBOV 24 hours later. Initial IFNγ dose response studies indicated that mice pretreated with 10 μg of IFNγ were better protected against MA-EBOV than treatment with 3 μg (S9A Fig). Thus, in subsequent studies, mice challenged with MA-EBOV were administered 10 μg of IFNγ. Since IFNγ given 48 hours following infection did not protect IFNAR -/mice against EBOV GP/rVSV (Fig 5A) , in these studies we assessed the protection IFNγ conferred against MA-EBOV when administered 24 hours prior to, at the time of infection, 6 or 24 hours following infection. All IFNγ-treated mice, regardless of time of treatment, had significantly less morbidity and mortality than untreated, infected mice, with treatment as late as 24 hours following infection protecting 100% of the mice from death (Fig 6A and 6B) . Lower MA-EBOV viremia levels were observed in the 24 hour post challenge treated mice, but not in the 24 hour pre-infection treatment group, suggesting that IFNγ administration as a post-exposure antiviral may prove more efficacious than when used prophylactically (Fig 6C) .