Our group has documented that DENV is a weak inducer of type I interferon in human DCs, in particular when compared with other viruses that competently produce these cytokines in large amounts, such as Newcastle disease virus (NDV) [22] and Semliki Forest virus (SFV) [23] . This lack of type I IFN production by DCs infected with DENV results in an impaired ability of those DCs to prime T cells toward Th1 immunity, an effect that can be reversed by the addition of IFNb [24] . Nevertheless, DENV is able to induce the expression of some pro-inflammatory cytokines at early times post infection, which we hypothesize is a strategy used by this virus to attract more cells to the site of infection by allowing the expression of some chemo-attractants by infected cells. Our group described that the infection by DENV does not induce the phosphorylation of IRF3 in human primary cells, resulting in an inhibition of type I IFN production [24] . In a subsequent report, we examined the ability of DENV-infected DCs to respond to a variety of type I IFN-triggering signals using potent stimulators such as NDV, SeV, SFV, or TLR-3 ligand poly(I:C) [25] . This effect is viral dose dependent and takes place as early as 2 hours after DENV infection. We also showed that the inhibition of IFNa/b production after NDV infection in DENV-infected DCs is not a bystander effect, implying an active role of the DENVinfected DC population in the inhibition of IFNa/b. By using an NDV vector strategy to express the individual DENV nonstructural proteins (NS2A, NS2B3, NS4A and NS4B), we showed that only the recombinant NDV expressing the protease complex NS2B3 inhibited IFNa expression in infected MDDCs, as compared to NDV alone. Similar results were obtained using an IFNb promoter activity assay in 293T cells. Catalytically inactive NS2B3 mutants showed a diminished inhibition of this phenotype, which highlighted the important role for the protease activity of the NS2B3 protein as inhibitor of the type I IFN production. Interestingly, the proteolytic core of NS2B3, consisting of the last 40 amino acids of NS2B and the first 180 amino acids of NS3, was enough to reduce the activation of the IFNb promoter by a strong stimulus, such as Sendai virus (SeV) infection.