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Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections

Departments of Surgery & Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2019, 11(12), 1097; https://doi.org/10.3390/v11121097
Received: 28 October 2019 / Revised: 19 November 2019 / Accepted: 25 November 2019 / Published: 27 November 2019
(This article belongs to the Special Issue Viral Evasion or Suppression of Host Immunity)
The sphingosine 1-phosphate (S1P) metabolic pathway is a dynamic regulator of multiple cellular and disease processes. Identification of the immune regulatory role of the sphingosine analog FTY720 led to the development of the first oral therapy for the treatment of an autoimmune disease, multiple sclerosis. Furthermore, inhibitors of sphingosine kinase (SphK), which mediate S1P synthesis, are being evaluated as a therapeutic option for the treatment of cancer. In conjunction with these captivating discoveries, S1P and S1P-metabolizing enzymes have been revealed to display vital functions during virus infections. For example, S1P lyase, which is known for metabolizing S1P, inhibits influenza virus replication by promoting antiviral type I interferon innate immune responses. In addition, both isoforms of sphingosine kinase have been shown to regulate the replication or pathogenicity of many viruses. Pro- or antiviral activities of S1P-metabolizing enzymes appear to be dependent on diverse virus–host interactions and viral pathogenesis. This review places an emphasis on summarizing the functions of S1P-metabolizing enzymes during virus infections and discusses the opportunities for designing pioneering antiviral drugs by targeting these host enzymes. View Full-Text
Keywords: sphingosine 1-phosphate metabolizing enzymes; virus-host interactions; host defense mechanisms; innate immunity; sphingosine kinase; sphingosine 1-phosphate lyase; viral pathogenesis sphingosine 1-phosphate metabolizing enzymes; virus-host interactions; host defense mechanisms; innate immunity; sphingosine kinase; sphingosine 1-phosphate lyase; viral pathogenesis
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Wolf, J.J.; Studstill, C.J.; Hahm, B. Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections. Viruses 2019, 11, 1097.

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