We suspect that the NSs-mediated PKR downregulation activity is important for RVFV replication and survival in infected mammalian hosts. RVFV-infection in rhesus monkeys showed that type I IFN is detectable around 1 day post-infection in both clinically ill surviving monkeys and lethally infected monkeys, and one dead monkey even kept high titer of IFN (120 to 480 U/ml) from 1 day post-infection [46] . In fact, the best correlation with outcome was early detection of IFN and not necessarily the height of the response. NSs suppresses IFN-b mRNA transcription early in the course of infection in cultured cells [26, 45] . Our present data suggest that the early downregulation of PKR in RVFVinfected cells might contribute to the inhibition of type I IFN induction, because PKR is known to serve as a pathogenrecognition receptor [47] . Furthermore, some of the host pathogen-recognition receptors, e.g., toll-like receptors 3 and 7, in uninfected cells located near the RVFV-infected cells, recognize virus-specific signals, e.g., viral RNAs in the virus particles or viral dsRNAs in the cell debris from infected cells, leading to type I IFN production. Because the transcriptional promoter of the PKR gene contains an IFN-stimulated response element, and IFN stimulation induces PKR mRNA transcription [38] , PKR abundance is likely increased in many uninfected cells of infected animals; RVFV needs to replicate in such cells to survive in infected hosts. The reduction in PKR abundance occurred as early as 4 h.p.i. ( Figure 7G ) and the NSs protein is produced very early in RVFV infection [48] . Immediate NSs synthesis and subsequent NSsinduced PKR downregulation in the cells, some of which have increased PKR abundance, could rapidly disarm the PKRmediated, antiviral functions and contribute to RVFV replication and survival in animal hosts.