It was reported that treatment of a macrophage cell line with IFN-c induced PKR degradation [62] . Because NSs induced PKR degradation in ActD-treated cells and ActD treatment completely inhibited the IFN-c mRNA accumulation ( Figure 6C ), it is highly unlikely that IFN-c was involved in the NSs-induced PKR downregulation. PKC activation also potentially induces PKR downregulation [41] . Treatment of MP-12-infected cells with a PKC inhibitor, GÖ 6983, did not inhibit NSs-mediated PKR downregulation ( Figure 7D ), which implied that PKC was not involved in it. Experiments using a proteasome inhibitor suggested that the NSs promoted PKR degradation through a proteasome pathway ( Figure 7F ). MG132 can induce GCN activation and translational suppression [42] . In fact, treatment of MP-12infected cells with MG132 and lactacystin moderately reduced the accumulation of NSs ( Figure 7F and 7G) . Accordingly, a possibility still exists that the MG132-induced moderate translational inhibition affected the NSs-induced PKR degradation in MG132-treated cells. For example, if the NSs-induced PKR downregulation requires an unstable host protein, then the MG132-induced moderate translational suppression would prevent accumulation of this putative host protein, resulting in inhibition of the NSs-induced PKR downregulation. Obviously further studies are required to elucidate the mechanism of PKR downregulation mediated by RVFV NSs.