A viral mechanism for inhibition of the cellular phosphatase calcineurin

Science. 1998 Jul 24;281(5376):562-5. doi: 10.1126/science.281.5376.562.

Abstract

The transcription factor NFAT (nuclear factor of activated T cells) controls the expression of many immunomodulatory proteins. African swine fever virus inhibits proinflammatory cytokine expression in infected macrophages, and a viral protein A238L was found to display the activity of the immunosuppressive drug cyclosporin A by inhibiting NFAT-regulated gene transcription in vivo. This it does by binding the catalytic subunit of calcineurin and inhibiting calcineurin phosphatase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Swine Fever Virus / physiology*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcineurin / metabolism
  • Calcineurin Inhibitors*
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cyclosporine / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Reporter
  • Macrophages, Alveolar / virology*
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Recombinant Proteins / metabolism
  • Swine
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Vero Cells
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • A238L protein, African swine fever virus
  • Calcineurin Inhibitors
  • DNA-Binding Proteins
  • NF-kappa B
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Viral Proteins
  • Cyclosporine
  • Calcineurin