Effects of interaction between parvovirus minute virus of mice NS1 and coactivator CBP on NS1-and p53-transactivation

The non-structural protein NS1, encoded by the parvovirus minute virus of m ice (MVM), is a potent regulator of viral gene expression in addition to pr ominent roles in viral replication and cytopathic effects associated with p arvoviral infection. Although NS1 involves the modulation of viral and cell ular transcription, the primary activation mechanism of MVM NS1 remains unc lear. In the present study, we show here that the coactivator CREB binding protein, CBP, could potentiate NS1-mediated transcription as measured on th e P38 promoter, which drives expression of the MVM capsid genes. NS1 bound to the two related cysteine-histidine-rich regions of CBP, referred to as C /H1 and C/H3, the former of which has an antagonistic function to CBP upon the NS1-transactivation. Furthermore, NS1 inhibited the synergistic transac tivation by CBP and p53. These findings suggested that CBP as a transcripti onal coactivator is required for NS1-mediated viral and cellular transcript ion in parvovirus-infected cells, resulting in cell proliferation and diffe rentiation to achieve its lytic cycle.