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

IFNγ reduced viral RNA levels in a manner similar to that observed with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ inhibits one or more viral life cycle events at or downstream of translation. ISGs have previously been identified to block viral protein translation, including the oligoadenylate synthetases [61] and indoleamine 2,3-dioxygenase [62] ; however, to date, none of these has been assessed for their ability to inhibit EBOV replication. Expression of both of these ISGs was significantly increased in our IFNγ-stimulated macrophages and likely contributed to the inhibition of EBOV infection that we observed. IFNγ is produced by several different hematopoietic cell types including natural killer cells, natural killer T cells and T lymphocytes [63, 64] . IFNγ induces specific cytotoxic and antiviral immunity by direct ISG production and through indirect mechanisms that likely provide additional mechanisms of action benefiting its clinical profile [19] . These added effects include IFNγ assisting in the activation of the adaptive immune system. IFNγ/receptor interactions lead to the up-regulation of phagocytosis, antigen processing and presentation in DCs and macrophages driving production of the Th1 phenotype of CD4+ T cells [19] . The relative importance of each of this diverse array of downstream effects on EBOV infection still needs to be elucidated.