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.
Miskin
J E
JE
Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey, GU24 0NF, UK.
Abrams
C C
CC
Goatley
L C
LC
Dixon
L K
LK
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