FIGURE 1.

Lipids and the replicative cycle of flavivirus. Flaviviruses depend on lipid metabolism to complete their replication cycle. (A) The membranes of Flaviviruses show a different composition than other cell membranes. Lipidomic, computational and functional studies suggest that flavivirus membranes are enriched with glycerophospholipids, sphingolipids, fatty acids, and cholesterol, all of which confer stability and robustness to the virion. During viral entry, contact with receptors allows internalization of the virion into the cell. These cellular receptors are usually coupled to lipid rafts in membranes with well-defined cholesterol concentrations and other membrane-stabilizing elements. (B) The viral genome release occurs in late endosomes using compartment-specific lipids. Lipids such as phosphatidylserine and phosphatidylethanolamine are involved in viral binding, entry, and fusion processes. (C) The viral RNA is translated into a polyprotein in the ER, which functions as a viral translation, replication, and morphogenesis platform. Infection-induced metabolic reprogramming leads to the accumulation of lipids required for viral replication. Lipid requirements are virus-dependent and cell-dependent; however, cholesterol and fatty acids appear necessary for the flavivirus cycle. (D) The involvement of lipid droplets (LDs) has been reported during viral replication and assembly. The co-localization and interaction of protein C with LDs have also been described during WNV, DENV, JEV, and ZIKV infections. (E) Finally, immature viral particles travel through the Golgi apparatus to complete their maturation process.