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 studies have only begun to identify IFNγ-stimulated proteins that contribute to the control of EBOV infection. Studies with type I IFNs have shown that a subset of ISGs preferentially target negative strand RNA viruses [51] and this may be the case with IFNγ-stimulated ISGs as well. Not surprisingly, expression of IFNγ-activated transcription factor IRF1 inhibited EBOV infection and this ISG served as a positive control in these experiments [18, 40, 52] . Other downstream ISGs were selected for study based on the enhancement of their expression elicited by IFNγ in our gene array studies and availability of expression constructs. The ability of GBP5, RARRES3 and VAMP5 to inhibit negative strand RNA viruses has been poorly studied and the mechanisms driving inhibition of virus replication remain to be elucidated. Each of these ISGs reduced EBOV infection; however, as has been shown with other viruses, combinations of ISGs are likely to provide additive or even synergistic inhibition if the ISGs are targeting independent modulatory pathways [40] .