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

Our results are the first to demonstrate the ability of IFNγ to protect animals both prophylactically and therapeutically against EBOV infection and suggest that this FDA-approved drug may be a useful antiviral for individuals with recent high-risk exposure. IFNγ treatment profoundly inhibited EBOV infection of peritoneal macrophages in tissue culture, consistent with the protection conferred by IFNγ and evidence that this cell type is an important early target for virus replication. Since antiviral efficacy required the presence of IFNγ receptor, but not the type I receptor, IFNγ control of EBOV infection occurs independently of type I IFN responses. Thus, we sought to identify specific IFNγ-stimulated genes involved in its antiviral effect. In addition to previously characterized ISGs, we identified three novel IFNγ-stimulated factors, GBP5, RARRES3 and VAMP5. To date, GBP5, RARRES3 or VAMP5 has not been shown to control negative strand RNA virus infection. Finally, we demonstrated that the recombinant BSL2-level virus, EBOV GP/rVSV, recapitulates our findings with EBOV, arguing that studies with this BSL2 model virus may serve as a safer and cost effective alternative for initial evaluations of novel anti-filoviral agents. Antiviral activity conferred by IFNγ against members of the Mononegavirales has been previously reported. For instance, addition of Pteropus alecto IFNγ to bat cells protects against the paramyxoviruses, Semiki forest virus and Hendra virus [47] . Additionally, several lines of evidence indicate that IFNγ is effective against rabies virus in tissue culture and in vivo, potentially through stimulation of type I IFN pathways [48, 49] .