Lipids and pathogenic flaviviruses: An intimate union

Flaviviridae: A growing family of human pathogens Among the major contributors to the positive-strand RNA virus global disease burden are the flaviviruses, a genus of enveloped viruses that includes Yellow fever virus (YFV), Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV) and is closely related to Hepatitis C virus (HCV) [2]. 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. https://doi.org/10.1371/journal.ppat.1006952.g001 Replication complex assembly remakes the host lipid landscape Inducing the negative membrane curvature required for vesicle formation is a thermodynamically unfavorable process [16]. [...]LD lipids may be required for multiple aspects of flavivirus infection and pathogenesis, from providing the raw materials and energy for replication to supporting efficient encapsidation and assembly of viral particles. Fatty acid synthesis is regulated by sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors also responsible for controlling cholesterol biosynthesis [30].