Murine gammaherpesvirus 68 Rta-dependent activation of the gene 57 promoter

The Rta homolog encoded by murine gammaherpesvirus 68 (γHV68) gene 50 is essential for virus replication and is capable of driving virus reactivation from the S11 latently infected B lymphoma cell line. Here we characterize Rta activation of γHV68 gene 57, which is abundantly transcribed during the early phase of virus replication. Infection of murine fibroblasts with an Rta null virus demonstrated that transcription of gene 57 is dependent on Rta expression. Analysis of the gene 57 promoter identified 2 distinct regions that are Rta responsive, either in the context of the gene 57 promoter or when cloned upstream of a heterologous promoter. Sequence analysis of these regions revealed homology to known Rta-responsive cis-elements in the closely related Kaposi's sarcoma-associated viral (KSHV) genome. In addition, two candidate binding sites for the cellular transcription factor RBP-Jκ/CBF1 were also identified in one of the Rta-responsive regions, which may play a role in mediating Rta transactivation similar to that observed in some KSHV Rta-responsive genes. Overall, analysis of the γHV68 gene 57 promoter suggests that mechanisms of Rta activation are conserved among γ2-herpesviruses.