Regulation of cellular and viral protein expression by the Epstein-Barr virus transcriptional regulator Zta: Implications for therapy of EBV associated tumors

Abstract

EBV encoded immediate-early proteins Zta is a member of the family of basic-leucine zipper (bZIP) transcription factors. It plays a critical role in both viral gene transcription and viral replication. As a lytic switch transactivator Zta regulates the expression of many early lytic genes. By binding to Zta responsive elements (ZREs) and TPA responsive elements (TREs) in the promoters of cellular genes or by interacting physically with cellular transcription factors, Zta also actively affects the expression of a variety of cellular genes that are fundamentally linked to the viral life cycle, cell cycle progression, cell growth, differentiation and apoptosis. Elucidation of the molecular mechanisms of regulating cellular protein by Zta in lytic program should not only increase our knowledge of interactions between EBV and host cells but also facilitate the development of anti-viral therapy strategies. A global investigation of cellular genes influenced by Zta and detailed exploration of alteration of cell activities during EBV lytic cycle will help to thoroughly illuminate the mechanisms of EBV persistence in host cells. Reactivation of the latent viral genome in EBV associated cancers can cause cancer cell death. Phosphorylation of ganciclovir and other antiviral nucleoside analogues by lytic cycle viral kinases can result in killing EBV positive tumor cells. Enforced expression of Zta could induce cell cycle arrest in several tumor cell lines. An intervention that leads to activation of lytic cycle viral kinases might facilitate the development of novel anti-tumor therapeutics.