Ceramide and Related Molecules in Viral Infections

Abstract

Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit.

Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

“…JEV in one of enveloped RNA viruses which can caused human severe central system infection diseases,the life cycle of this viruses is critically dependent on host lipid biosynthesis [22] ,pivotal biological function of lipid metabolism during JEV infection [23] .From viral binding and entry,infection by these viruses leads to reorganization of cellular membranes and lipid metabolism to support the production of new viral particles [24,25] . Recent work has focused on de ning the involvement of speci c lipid classes in above process in hopes of identifying potential therapeutic targets for the treatment or prevention of disease.…”

Diversity of Lipid Function in Atherogenesis: A Focus on Endothelial Mechanobiology

“…Inhibition of acid sphingomyelinase and ceramide formation has been shown to improve endothelium-dependent vasodilation in diabetic animals [ 224 ]. Drugs belonging to the group of functional inhibitors of acid sphingomyelinase (FIASMA) are considered as promising agents for the treatment of many diseases associated with increased acid sphingomyelinase activity, but data on their role in atherogenesis are limited, highlighting the need for better study [ 225 , 226 , 227 ]. The complex role of sphingomyelinases in mechanotransduction is demonstrated by the fact that inhibition of neutral rather than acidic sphingomyelinase by scyphostatin results in impaired shear stress-induced mechanotransduction, demonstrating the involvement of neutral sphingomyelinase and ceramide formation as a primary and secondary mediator of downstream mechanosensory signal transduction.…”

Sphingolipids: Effectors and Achilles Heals in Viral Infections?

“…As their amplification is strictly intracellular, the interaction of viruses with cellular membranes is a key component of their life cycle, and this also includes availability and composition of most prominent membrane lipids such as SLs. The role of steady state SL metabolism and that regulated by pathogens in their respective host cells has been studied in the more recent past (for a recent review see [ 38 ]). This has been greatly advanced by progress made in terms of high resolution quantitative analysis and microscopy (see above) and implementation of functionalized SLs, allowing the study of topological accumulation in cellular compartments in the context of viral infection (recently reviewed in [ 39 ]).…”