English: Replication cycle of Japanese encephalitis virus (JEV). A viral particle binds initially to a target cell through one or more attachment factors on the cell surface (Attachment). Subsequently, the virion interacts with an entry factor(s), which triggers receptor-mediated clathrin-dependent or clathrin-independent endocytosis of the bound virion (Endocytosis). Following internalization, the virion travels through the endosomal maturation pathway until endosomal acidification triggers the low pH-induced activation of the viral E glycoprotein, enabling the fusion between viral and endosomal membranes (Membrane fusion). Upon release of the viral genomic RNA into the cytoplasm (Uncoating), it is translated into two overlapping polyproteins as the result of a −1 ribosomal frameshift event in association with the ER (Translation). The polyproteins are co- and post-translationally cleaved to generate the mature viral proteins that are essential for RNA replication and virion assembly. The genomic RNA is replicated in the replication complex within a structurally rearranged ER-derived membrane vesicles (RNA replication). Viral assembly proceeds with the concomitant interaction of viral RNA with the three structural proteins (C, prM, and E), promoting the budding of immature particles into the lumen of the ER (Assembly). The immature virions, containing heterodimers of prM and E, are then transported through the trans-Golgi network, where prM is cleaved to form mature virions containing homodimers of M and E (Maturation). Finally, both partially and completely mature virions are released into the extracellular milieu (Release).