Lipids and pathogenic flaviviruses: An intimate union
After flavivirus particles are internalized through receptor-mediated endocytosis, fusion with the membrane of the late endosome releases a single positive-sense RNA genome into the cytoplasm of the host cell. Translation by cellular ribosomes results in membrane-associated structural and nonstructural proteins, which curve ER lipid bilayers into invaginated replication vesicles and budding sites (inset). To facilitate membrane remodeling and replication, flaviviruses manipulate multiple aspects of both structural and bioactive lipid classes in an organelle-dependent manner. The resulting dysregulation of cellular pathways may contribute to cell death and clinical disease. Fully assembled virus particles are transported to the Golgi apparatus, where they undergo a maturation process and are released through exocytosis. Cer, ceramide; Chol, cholesterol; DAG, diacylglycerol; ER, endoplasmic reticulum; FFA, free fatty acids; GalCer, galactosylceramide; GlcCer, glucosylceramide; GSPL, complex glycosphingolipids; mTOR, mammalian target of rapamycin; NS, nonstructural; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PIP2, phosphatidylinositol-(4,5)-bisphosphate; PI, phosphatidylinositol; PIP3, phosphatidylinositol-(3,4,5)-trisphosphate; PM, plasma membrane; PS, phosphatidylserine; S1P, sphingosine-1-phosphate; SM, sphingomyelin; TAG, triacylglycerol; Ve, invaginated vesicles.