The past studies [25, 26, 45] and the data shown in this study illustrate that two distinct biological activities of the RVFV NSs protein worked together to secure efficient RVFV replication. Namely, nuclear NSs protein inhibits transcription of host mRNAs, including the IFN mRNAs; this activity is critical for efficient RVFV replication in IFN-competent systems [25, 45] . However, a combination of RVFV replication and NSs-mediated host mRNA transcriptional suppression possibly induces PKR activation and subsequent eIF2a phosphorylation as a combination of RVFV replication and ActD or a-amanitin treatment induced it. The NSs protein, in turn, promotes PKR downregulation as early as 4 h.p.i., and prevents eIF2a phosphorylation to secure the translation of viral mRNAs and efficient virus replication. We think that both of these two NSs functions are tightly related and protect efficient viral replication by suppressing host antiviral responses. In RVFV-infected cells, the NSs establishes general transcriptional suppression at a later stage of infection (after 8 h.p.i.) [25] , while NSs also suppresses specific IFN-b mRNA transcription at early stages of infection (about 3 h.p.i.) by maintaining repressor complex including SAP30 on IFN-b promoter [26, 45] . PKR downregulation early in infection is probably important for maintaining efficient viral translation in combination with the suppression of host IFN responses.