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

Viruses. 2019 Nov 27;11(12):1097. doi: 10.3390/v11121097.

Abstract

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.

Keywords: host defense mechanisms; innate immunity; sphingosine 1-phosphate lyase; sphingosine 1-phosphate metabolizing enzymes; sphingosine kinase; viral pathogenesis; virus-host interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aldehyde-Lyases / antagonists & inhibitors
  • Aldehyde-Lyases / immunology*
  • Antiviral Agents / immunology
  • Antiviral Agents / therapeutic use
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate*
  • Interferon Type I / therapeutic use
  • Lysophospholipids / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / immunology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Virus Diseases / immunology*
  • Virus Diseases / virology
  • Virus Replication
  • Viruses / enzymology*
  • Viruses / genetics
  • Viruses / immunology
  • Viruses / pathogenicity

Substances

  • Antiviral Agents
  • Interferon Type I
  • Lysophospholipids
  • sphingosine 1-phosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Aldehyde-Lyases
  • sphingosine 1-phosphate lyase (aldolase)
  • Sphingosine