Abstract
Several notable human diseases are caused by enveloped RNA viruses: Influenza, AIDS, hepatitis C, dengue hemorrhagic fever, microcephaly, and Guillain–Barré Syndrome. Being enveloped, the life cycle of this group of viruses is critically dependent on host lipid biosynthesis. Viral binding and entry involve interactions between viral envelope glycoproteins and cellular receptors localized to lipid-rich regions of the plasma membrane. Subsequent infection by these viruses leads to reorganization of cellular membranes and lipid metabolism to support the production of new viral particles. Recent work has focused on defining the involvement of specific lipid classes in the entry, genome replication assembly, and viral particle formation of these viruses in hopes of identifying potential therapeutic targets for the treatment or prevention of disease. In this review, we will highlight the role of host sphingolipids in the lifecycle of several medically important enveloped RNA viruses.
Highlights
Human viruses come in various shapes and sizes with DNA or RNA as their genetic material.The focal point of this review is on enveloped RNA virus particles, which consist of a lipid bilayer typically surrounding the genomic-RNA-protecting shell or capsid
In another study from our laboratory, we found that hepatitis C virus (HCV) redirects the glycosphingolipid carrier protein, FAPP2 (Figure 1), to the membranous web to facilitate HCV genome replication [20]
The role of sphingolipids and glycosphingolipids has been overlooked for many years in viral infection due to the difficulty of detecting or measuring these lipids
Summary
Human viruses come in various shapes and sizes with DNA or RNA as their genetic material. Most positive-stranded RNA viruses replicate exclusively in the cytoplasm of the infected cell and in intimate contact with intracellular membranes. This strategy enables viral and host factors to concentrate in distinct cellular locations to optimize a new virus particle’s formation and evade innate immune responses [4,5,6,7,8]. Sphingolipids and glycosphingolipids have been detected with state-of-the-art liquid chromatography coupled with mass spectrometry (e.g., LC-MS/MS system) This approach has enabled investigators to accurately determine the levels of sphingolipid and glycosphingolipid species in cells or tissues [28,29] and the impact of viral infection on levels of these lipids [30]. SGMS1/2: sphingomyelin synthase; GCS: glucosylceramide synthase; B4G5: lactosylceramide synthase; ST3GAL5: lactosylceramide alpha-2,3-sialyltransferase or GM3 synthase; A4GalT: alpha 1,4-galactosyltransferase or Gb3 synthase; SPT: serine palmitoyl transferase; CERT: ceramide transfer protein; FAPP2: four-phosphate adaptor protein 2; GlcCer: glucosylceramide; LacCer: lactosylceramide
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