The newly synthesized Dengue virus (DENV) positive-sense RNA (+ssRNA) genomes are packaged into viral particles in the endoplasmic reticulum (ER), where they associate with the structural viral proteins C, prM, and E (reviewed in Rodenhuis Zybert et al. 2010). The immature viral particles are transported through the Golgi apparatus to exocytic vesicles, where prM is cleaved to form mature virions. In mature virions, E is organized as 90 head-to-tail orientated dimers of E:M heterodimers, which lie in sets of three, nearly parallel to each other and to the viral surface, forming a smooth ‘‘herringbone’’ configuration (E:M:M:E; reviewed in Rodenhuis-Zybert et al. 2010). Three E:M:M:E tetramers present in each icosahedral asymmetric unit exist in three chemically distinct environments and may therefore play a distinct role in different stages of the infection (reviewed in Rodenhuis-Zybert et al. 2010; Pierson & Diamond, 2012; Apte-Sengupta et al., 2014). The mature virions are released from the cell via exocytosis.