To establish that RVFV NSs exhibits a novel function, we hypothesized that, when combined, RVFV replication and NSsinduced host transcription suppression likely induces a cellular environment that is unsuitable for viral replication. Thus, to secure efficient RVFV replication, the NSs protein, in turn, alters this putative, virally unfriendly cellular environment to one that supports efficient viral replication. To test this possibility, we examined the replication of RVFV lacking the NSs gene, a mutant which was generated by employing a reverse genetics system [19] , in the presence of a host transcription inhibitor, e.g., actinomycin D (ActD) or a-amanitin; these drugs were selected because they mimicked the host transcriptional suppressive activities of the NSs. Consistent with our supposition, RVFV lacking the NSs, but not RVFV, failed to replicate efficiently in ActD-treated cells. We noted that double-stranded RNA (dsRNA)-dependent protein kinase (PKR)-mediated eukaryotic initiation factor (eIF)2a phosphorylation suppressed the translation of RVFV lacking NSs in the presence of ActD. Further studies uncovered that RVFV NSs promoted PKR downregulation as early as 4 hours post-infection, and prevented eIF2a phosphorylation, which secured efficient viral translation. We speculate that this novel function of RVFV is important for counteracting the antiviral activities of PKR and allowing efficient virus replication and survival in infected hosts.