African swine fever virus protein A238L interacts with the cellular phosphatase calcineurin via a binding domain similar to that of NFAT

The African swine fever virus protein A238L inhibits activation of NFAT tra nscription Factor by binding calcineurin and inhibiting its phosphatase act ivity. 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(PxTxITxC/S) required for A238L binding to calcineu rin; a similar motif is found in NFAT proteins. Peptides corresponding to t his domain of A238L bind calcineurin but do not inhibit its phosphatase act ivity. Binding of A238L to calcineurin stabilizes the A238L protein in cell s. Although A238L-mediated suppression of NF-KB-dependent gene expression o ccurs by a different mechanism, the A238L-calcineurin interaction may be re quired to stabilize A238L.