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

As a control for these studies, we also evaluated the ability of IFNγ to protect against wildtype VSV infection. Initial studies demonstrated that equivalent concentrations of VSV were more virulent in mice than our recombinant virus, EBOV GP/rVSV, perhaps because of the broad cellular tropism conferred by the native VSV glycoprotein G [44, 45] . As a consequence, in these studies we used 10 2 infectious units of VSV as our challenge virus, the lowest concentration of VSV that resulted in predictable death. IFNAR -/mice challenged with VSV were given 3.3 μg of IFNγ either 24 hours prior or 2 hours after challenge. While the 24-hour pretreated mice had significant protection, 40% mortality was still observed. Surprisingly, the survival of the 2-hour IFNγ post-treatment mice was not significantly different from the PBStreated, VSV infected mice (S8B Fig) . This finding stands in contrast to the robust protection IFNγ conferred at 2, 6 and 12 hours following EBOV GP/rVSV challenge. These findings suggested that VSV infection is less sensitive to IFNγ, particularly when administered as a postchallenge antiviral.