DENV is a single stranded RNA virus of positive polarity that, after entering the cytoplasm of the host cell, releases its genome and synthesizes a polyprotein using the cellular machinery, as a first event of the viral cycle. The DENV polyprotein is cleaved by the viral protease complex (NS2B3) and cellular proteases, including furin [8] . After this processing, some of the viral proteins have the ability to rearrange the ER membrane and create the micro-environment necessary for the production of de novo synthesized viral genomic RNA. During this event, DENV accumulates products with conserved molecular structures, like RNA with 59-triphosphate moiety or double stranded RNA, also referred to as pathogen associated molecular patterns (PAMPs). These foreign molecules are ligands of different cellular receptors engaged in their recognition, known as pattern recognition receptors (PRRs). PRRs are mainly divided into two different classes depending on their localization, associated with either the membrane or the cytoplasm. The Toll-like receptor (TLR) family is composed of membrane proteins with domains that are designed to detect extracellular PAMPs. On the other hand, the cytosolic DExD/Hbox RNA helicase proteins that contain caspase-recruiting domains (CARDs), referred to as RIG-I and MDA-5, can detect specific PAMPs present in the cytoplasm. These last two cytoplasmic sensors together with the TLR family members (TLR3/TLR7/TLR8) have been described so far as the most relevant DENV sensors [9, 10, 11] . After recognition of the mentioned PAMPs by the C-terminal helicase domain of RIG-I and MDA-5, these undergo a conformational change that exposes their CARD domains and promote the interaction with different down-stream molecules. One of the most well studied downstream molecules, referred as IPS-1 (also known as, MAVS, CARDIF or VISA), is located in the outer membrane of the mitochondria and transmits the signal via different molecules, including the tumor necrosis factor receptor associated factors 6 and 3 (TRAF6 and TRAF3) and the IkB kinase (IKK) family members (TBK1, IKKa, IKKb and IKKe) among other cellular factors [reviewed in [12] ]. Recently three different groups, using cDNA library screening of genes that induced the IFNb promoter, described an adaptor protein that localizes in the endoplasmic reticulum (ER). This protein was named as stimulator of the interferon gene (STING) [13] , mediator of IRF3 activation (MITA) [14] and endoplasmic reticulum IFN stimulator (ERIS) [15] . Also the same protein, referred to as MYPS, was previously identified as a mediator of anti-major histocompatibility complex II monoclonal antibody-induced apoptosis in B-lymphoma cells [16] . STING is highly expressed in several immune cells, including macrophages and DCs, as well as endothelial and epithelial cells [13] . This protein can interact with RIG-I and IPS-1, but not with MDA-5, and the signaling mediated by this adaptor is independent of the sensing by the TLR family members [17] . In two recent reports, it was documented that STING is involved in the pathway that mediates the detection of pathogens with DNA genomes [18] and has a role as a direct sensor of cyclic dinucleotides, a signaling molecule produced exclusively by bacteria and archea [19] . Activation of STING by some of these stimuli leads to its relocalization with TBK1 from the ER to perinuclear vesicles containing the subunit of the exocyst complex 5 (Sec5) followed by the phosphorylation of TBK-1 and the subsequent activation of the transcription factors IRF3/7 and NFkB, which translocate to the nucleus and complex with ATF2/c-Jun to induce the expression of type I IFN and pro-inflammatory cytokines [17] .