To validate the results described using p55-C1B and IFNb promoter assays in a primary cell model, we measured IFNa/b production upon infection of MDDCs either with DENV or a Semliki forest virus (SFV) expressing the DENV NS2B3 protease complex or the mutant version of the protease (NS2B3-S135A) as a control [23, 25] . Consistent with our earlier report [24] , human MDDCs infected with DENV-2 (16681 strain) were unable to produce IFNa/b. Furthermore, SFV-NS2B3 induced significantly lower levels of IFNa/b mRNA than the SFV-NS2B3-S135A ( Figures 3A and 3B ). Interestingly, SFV-NS2B3-WT induced significantly higher expression of TNFa at early times postinfection compared to SFV-NS2B3-S135A control ( Figure 3C ). As shown previously, this would suggest an involvement of the NS2B3 protease complex in the expression of this pro-inflammatory cytokine [24] . As expected, the infection of MDDCs by DENV upregulated the expression of STING in these cells ( Figure 3D ). Figure 3E shows the kinetics of infection by DENV in MDDCs, with the peak of viral RNA at 48 hpi. In contrast, the SFV vectors used in these studies show low levels of viral RNA at late times after treatment ( Figure 3F ), since these vectors are replication deficient [36] . Then we infected mouse bone marrow-DCs (BM-DCs) using the same viruses, and analyzed the gene induction profile in those cells. As expected, infection of BM-DCs by DENV was rapidly controlled, consistent with the inability of DENV to infect mouse cells, and showed an opposite kinetic of viral RNA synthesis compared to the observed pattern in human DCs, with a modest induction of cytokines ( Figure 3G to 3K). SFV is an alphavirus that can replicate in mouse cells, and DCs in particular. In this context, the SFV-NS2B3 exhibited a higher induction of both IFNa/b genes compared to the SFV-NS2B3-S135A control, showing an opposite profile than that observed in human DCs, in which SFV-NS2B3-S135A induced higher levels of IFNa/b genes ( Figure 3G and 3H) . Again, the kinetics of infection of the SFV vectors in mouse DCs ( Figure 3L) show very low levels of viral RNA, consistent with their lack of productive infection in these cells [36] . The observed phenomenon agrees with the inability of recombinant DENV-NS2B3 to cleave mouse STING and decrease the activity of the IFNb and p55-C1B promoters induced by this adaptor protein ( Figure 2C and 2D).