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

Here, we demonstrate that IFNγ blocks EBOV infection of murine peritoneal macrophages and robustly protects mice from fatal EBOV infection when administered as late as 24 hours following infection. We also identified novel IFNγ-stimulated genes that inhibit EBOV infection, defining new downstream mechanisms through which this FDA-approved drug functions. During these studies, we evaluated IFNγ inhibition of a BSL2 model virus of EBOV, recombinant vesicular stomatitis virus (VSV) encoding EBOV glycoprotein (EBOV GP/rVSV), in interferon α/β receptor knock out (IFNAR -/-) mice. IFNγ was highly effective at inhibiting infection by this recombinant virus. Comparative use of this recombinant BSL2 virus in parallel with EBOV and wild-type VSV permitted us to evaluate the mechanism of IFNγ inhibition in greater detail. These latter findings suggest that IFNγ may have efficacy not only against EBOV, but also a broader range of Mononegavirales.