A viral mechanism for inhibition of the cellular phosphatase calcineurin.
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.
Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey, GU24 0NF, UK.
J E
JE
Miskin
C C
CC
Abrams
L C
LC
Goatley
L K
LK
Dixon
D000358:African Swine Fever Virus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D016676:Macrophages, Alveolar / Q000821:virology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C113585:A238L protein, African swine fever virus; D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D016572:Cyclosporine; D019703:Calcineurin