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

Gene expression of Mononegavirales viruses, including filoviruses and rhabdoviruses, is initiated by primary transcription of mRNAs that does not require new viral protein synthesis [33] . However, subsequent viral genome replication requires viral protein production and replication of the genome is blocked by inhibitors of protein synthesis such as cycloheximide (CHX) [34] . Therefore, to narrow down which step(s) within the life cycle is affected by IFNγ, we compared the ability of IFNγ and CHX to inhibit viral RNA production and determined if the combination of these two drugs inhibited viral RNA levels to a greater extent. BALB/c IFNAR -/peritoneal macrophages were treated with M-CSF in the presence or absence of IFNγ for 24 hours. At the initiation of EBOV infection under BSL4 conditions, CHX was added and viral RNA levels were assessed at 6 and 14 hours of infection. CHX or IFNγ suppressed EBOV nucleoprotein (NP) and polymerase (L) RNA levels equally and the combination of inhibitors did not further reduce EBOV RNA production ( Fig 2B) . Similar results were observed with EBOV GP/rVSV infections harvested at 6 hours (S4 Fig). In total, these findings indicate that IFNγ treatment interferes with RNA synthesis that is dependent upon protein synthesis and suggests that virus replication is blocked.