Abstract
In this review, we summarize the mechanisms by which sphingolipids modulate virus multiplication and the host innate immune response, using a number of host-virus systems as illustrative models. Sphingolipids exert diverse functions, both at the level of the viral life cycle and in the regulation of antiviral immune responses. Sphingolipids may influence viral replication in three ways: by serving as (co)receptors during viral entry, by modulating virus replication, and by shaping the antiviral immune response. Several studies have demonstrated that sphingosine kinases (SphK) and their product, sphingosine-1-phosphate (S1P), enhance the replication of influenza, measles, and hepatitis B virus (HBV). In contrast, ceramides, particularly S1P and SphK1, influence the expression of type I interferon (IFN-I) by modulating upstream antiviral signaling and enhancing dendritic cell maturation, differentiation, and positioning in tissue. The synthetic molecule α-galactosylceramide has also been shown to stimulate natural killer cell activation and interferon (IFN)-γ secretion. However, to date, clinical trials have failed to demonstrate any clinical benefit for sphingolipids in the treatment of cancer or HBV infection. Taken together, these findings show that sphingolipids play an important and underappreciated role in the control of virus replication and the innate immune response.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Highlight: sphingolipids in infectious biology and immunology
- Sphingolipids in early viral replication and innate immune activation
- The function of sphingomyelinases in mycobacterial infections
- The role of acid sphingomyelinase and modulation of sphingolipid metabolism in bacterial infection
- The neutral sphingomyelinase 2 in T cell receptor signaling and polarity
- Click reactions with functional sphingolipids
- Sphingolipids in inflammatory hypoxia
- CD4+ Foxp3+ regulatory T cell-mediated immunomodulation by anti-depressants inhibiting acid sphingomyelinase
- Pathological manifestations of Farber disease in a new mouse model
- Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin
- Minireview
- Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding
- Research Articles/Short Communications
- Proteolysis
- The two cathepsin B-like proteases of Arabidopsis thaliana are closely related enzymes with discrete endopeptidase and carboxydipeptidase activities
Artikel in diesem Heft
- Frontmatter
- Highlight: sphingolipids in infectious biology and immunology
- Sphingolipids in early viral replication and innate immune activation
- The function of sphingomyelinases in mycobacterial infections
- The role of acid sphingomyelinase and modulation of sphingolipid metabolism in bacterial infection
- The neutral sphingomyelinase 2 in T cell receptor signaling and polarity
- Click reactions with functional sphingolipids
- Sphingolipids in inflammatory hypoxia
- CD4+ Foxp3+ regulatory T cell-mediated immunomodulation by anti-depressants inhibiting acid sphingomyelinase
- Pathological manifestations of Farber disease in a new mouse model
- Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin
- Minireview
- Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding
- Research Articles/Short Communications
- Proteolysis
- The two cathepsin B-like proteases of Arabidopsis thaliana are closely related enzymes with discrete endopeptidase and carboxydipeptidase activities