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

In vivo IFNγ treatment protects IFNAR -/mice against lethal EBOV GP/ rVSV challenge, but is less efficacious against wild-type VSV Since IFNγ robustly inhibits EBOV GP/rVSV and EBOV infection of macrophages and macrophages are an important cellular target for filoviruses pathogenesis, we evaluated the ability of intraperitoneally (i.p.) administered IFNγ to protect mice against lethal i.p. challenge. For these studies, BALB/c IFNAR -/mice were used as little to no pathogenesis is observed with EBOV GP/rVSV infections of wild-type mice, but significant morbidity and mortality occurs in IFNAR -/mice. Initial IFNγ dose response studies demonstrated that both 3.3 and 10 μg of IFNγ protected IFNAR -/mice against lethal EBOV GP/rVSV challenge (S8A Fig). Further, neither dose of IFNγ had any detectable consequence on the weight or health of the mice. Therefore, subsequent studies were performed with both dosages. IFNγ administered by i.p. injection 24 hours prior to, 2 or 6 hours after a lethal dose of EBOV GP/rVSV protected mice against challenge, with treated mice demonstrating significantly reduced mortality, weight loss and clinical sickness scores compared to untreated, virus-infected animals (Figs 5A and S8B-S8D). At the 10 μg IFNγ dose, we also assessed survival of mice when IFNγ was given at 12 and 48 hours after challenge. While only 75% of the mice survived challenge in the 12-hour post challenge group, the protection offered by this treatment was not statistically different than that conferred at time points more proximal to the challenge (Fig 5A) . However, IFNγ administered 48 hours following EBOV GP/rVSV did not protect mice against lethal challenge.