By co-expression experiments of human STING with the DENV NS2B3 protease complex we observed a specific cleavage at (94-RRGA-99), a site described as a putative target for DENV NS2B3 [32] that generated a cleaved band of approximately 32 KDa (Figure 1C and 1F) . Interestingly, by analysis of the sequence alignment between human STING and its mouse version we, observed a drastic difference in the amino acid sequence in this region (94-HCMA-99) (shown in figure 1B ) and the inability to cleave the mouse STING by the DENV NS2B3 was confirmed by co-expression experiments ( Figure 1D and 1G) . Furthermore, the impact that the STING cleavage by NS2B3 had on the signaling of IFNb production pathway was subsequently demonstrated using IFNb and p55-C1B promoter systems ( Figure 2 ). In these experiments, a reduction in luciferase induction was only observed for human STING, suggesting that the cleavage confirmed by WB (showed in Figures 1C and 1F ) impaired the ability of this adaptor to induce IFNb. Recently, Jin et al. described a series of mutations in hSTING that were implicated in the activation/dimerization and subsequent induction of interferon. Interestingly, two cysteines located at C88XXC91 were fundamental for the proper induction of type I IFN after stimulation [33] . It could be interesting to investigate the presence of mutations at the cleavage site of STING for DENV NS2B3 in the human population, to identify a natural resistance to DENV infection.