Activation of T-cell-factor-dependent transcription by Kaposi's sarcoma-associated herpesvirus replication transactivation activator

Objective: To elucidate the cellular function of Kaposi's sarcoma-associated herpesvirus (KSHV) replication transactivation activator (RTA) at the transcriptional level. Methods: Transcriptional activation of T-cell-factor (TCF)-dependent genes by RTA was determined using the luciferase reporter assay. The specific regions of RTA required for the activation of TCF-dependent transcription and association with β-catenin were established. Results: RTA specifically activated TCF-dependent transcription in a dose-dependent manner, to an extent comparable to the activation achieved by latency-associated nuclear antigen. In contrast, other KSHV viral proteins investigated, such as basic leucine zipper and viral interferon regulatory factor 1, did not affect TCF-dependent transcription. The C-terminal region of RTA appeared to be necessary for transcription. However, RTA did not affect the β-catenin level or the subcellular localization thereof. Conclusion: Our results collectively demonstrate that KSHV RTA activates TCF-dependent transcription without involving the β-catenin pathway.