The Epstein-Barr virus BZLF1 protein interacts physically and functionallywith the histone acetylase CREB-binding protein

The Epstein-Barr virus (EBV) immediate-early protein BZLF1 (Z) is a key reg ulator of the EBV latent-to-lytic switch. Z is a transcriptional activator which induces EBV early gene expression. We demonstrate here that Z interac ts with CREB-binding protein (CBP), a histone acetylase and transcriptional coactivator. This interaction requires the amino-terminal region of CBP as well as the transactivation and leucine zipper domains of Z. We show that CBP enhances Z-mediated transactivation of EBV early promoters, in reporter gene assays and in the context of the endogenous genome. We also demonstra te that Z decreases CREB transactivation function and that this inhibitory effect is reversed by overexpression of CBP. We show that Z also interacts directly with CREB. However, mutational analysis indicates that Z inhibitio n of CREB activity requires the direct interaction between Z and CBP but no t the direct interaction between Z and CREB. We propose that Z interacts wi th CBP to enhance viral early gene transcription. In addition, the Z-CBP in teraction may control host cellular transcription factor activity through c ompetition for limiting amounts of cellular CBP.