DENV infects multiple organs and cell types in humans. Particularly, the mononuclear phagocyte lineage of macrophages, monocyte-derived dendritic cells (DCs) and skin Langerhans cells are the primary cell targets [4, 5, 6] . Similar cellular tropism of macrophages and DCs was observed in the experimental DENV mouse infection model [7] . Macrophages and DCs are the most crucial cell types in innate immunity and rapidly produce type I interferons (IFNs) and cytokines to fight against microbe invasion. Type I IFNs are potent inhibitors of virus replication. Therefore, many pathogenic viruses have developed strategies to escape the IFN-triggered anti-viral effects. More than 170 different virusencoded IFN antagonists from 93 distinct viruses have been described [8] . For example, hepatitis C virus (HCV), a member of Flaviviridae, evades innate immunity by cleaving mitochondrial antiviral signaling protein, an IFN stimulator, with its protease NS3/4A [9] . The nonstructural proteins NS4B of DENV-2, West Nile virus (WNV), and yellow fever virus (YFV) block the activation of STAT1 in cells stimulated with type I IFN [10, 11] .