The inability of DENV to replicate in wild type mouse cells is well documented, and many attempts have been made to develop a competent animal model to study DENV infection [50] . The data presented in this manuscript, showing the ability of DENV to replicate in Sting 2/2 MEF (Figure 4) , open new approaches to develop a mouse model to study DENV infection and also highlights the requirement that type I IFN production has on the innate immune system and for the control of invading pathogens. Ashour et al. described the adaptor STAT2 as a restriction factor for DENV replication in mouse cells [31] . Based on our combined data, an interesting approach would be the development of a transgenic mouse model with humanized STING and STAT2. This approach could provide an immune competent mouse model for DENV that eliminates two of the potential bottlenecks that exist for DENV replication in mice.