The position of the ZEBRA activation domain does not influence its biological activity.

Epstein-Barr virus (EBV) is a human herpesvirus which latently infects B lymphocytes. EBV encodes a unique transcriptional activator, known as ZEBRA, which can disrupt viral latency in B cells and induce lytic viral replication. Furthermore, ZEBRA has been shown to bind at the EBV origin of lytic replication, and is necessary for viral DNA replication to occur. Previously we demonstrated that heterologous activation domains can fully substitute for the ZEBRA activation domain. Here we extend those results by showing that the position of the ZEBRA activation domain or a heterologous replacement domain does not influence its ability to function in the disruption of EBV latency. In this study three novel clones were constructed in which the ZEBRA activation region was repositioned to the carboxy terminus of the protein. These mutants were used to demonstrate that the ability of ZEBRA's wild type domain to function in the complex biological process of virus activation is not compromised by altering its position within the protein.