The pathogenic arenaviruses have evolved strategies to suppress and evade the host immune response [25, 26, 27, 28] , resulting in uncontrolled replication and broad dissemination. However, they appear to be unable to block the induction of IFN stimulated genes via exogenous type I IFN [29] , which may, in part, explain the success of DEF201 and cIFN-a treatments [15] . Also essential to the success of DEF201 was early intervention prior to significant viral replication and engagement of innate immune suppressive functions. Indeed, early induction of a strong type I IFN response is associated with favorable disease outcome in nonhuman primates challenged with Lassa virus [30] . Early post-exposure prophylaxis was also required with exogenous cIFN-a protein administered by the i.p. route [15, 16] . With the multiple strategies that arena and other pathogenic viruses have in place to subdue the IFN-mediated host antiviral response [31] , the utility of DEF201, recombinant IFN proteins, and IFN inducing agents will depend upon the nature of the IFN pathway blockade and require early administration to be effective post-exposure.