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Journal of Virology, October 2000, p. 9412-9420, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

African Swine Fever Virus Protein A238L Interacts with the Cellular Phosphatase Calcineurin via a Binding Domain Similar to That of NFAT

James E. Miskin, Charles C. Abrams, and Linda K. Dixon*

Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey GU24 0NF, United Kingdom

Received 7 July 2000/Accepted 13 July 2000

The African swine fever virus protein A238L inhibits activation of NFAT transcription factor by binding calcineurin and inhibiting its phosphatase activity. NFAT controls the expression of many immunomodulatory proteins. Here we describe a 14-amino-acid region of A238L that is needed and sufficient for binding to calcineurin. By introducing mutations within this region, we have identified a motif (PxIxITxC/S) required for A238L binding to calcineurin; a similar motif is found in NFAT proteins. Peptides corresponding to this domain of A238L bind calcineurin but do not inhibit its phosphatase activity. Binding of A238L to calcineurin stabilizes the A238L protein in cells. Although A238L-mediated suppression of NF-kappa B-dependent gene expression occurs by a different mechanism, the A238L-calcineurin interaction may be required to stabilize A238L.

* Corresponding author. Mailing address: Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey GU24 0NF, United Kingdom. Phone: 44 1483 232441. Fax: 44 1483 232448. E-mail: linda.dixon{at}bbsrc.ac.uk.

Journal of Virology, October 2000, p. 9412-9420, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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