The Cellular Ataxia Telangiectasia-Mutated Kinase Promotes Epstein-Barr Virus Lytic Reactivation in Response to Multiple Different Types of Lytic Reactivation-Inducing Stimuli

• DOI: 10.1128/jvi.01850-12
• Publication Date: 2012-09-27T16:07:40Z
• Authors: Stacy R. Hagemeier; Elizabeth A. Barlow; Qiao Meng; Shannon C. Kenney
• Keywords: Lytic cycle; BZLF1; Virus latency

ABSTRACT The Epstein-Barr virus (EBV) latent-to-lytic switch is mediated by the viral proteins BZLF1 (Z), BRLF1 (R), and BRRF1 (Na). Since we previously showed that DNA-damaging agents (including chemotherapy irradiation) can induce EBV lytic reactivation recently demonstrated wild-type p53 contributes to reactivation, investigated role of ATM kinase during reactivation. phosphorylates activates p53, as well numerous other substrates involved in cellular DNA damage response. Using an inhibitor (KU55933), found activity required for efficient induction gene expression a variety different stimuli, including histone deacetylase (HDAC) inhibitor, transforming growth factor β (TGF-β) cytokine, demethylating agent (5-azacytidine), B cell receptor engagement with anti-IgG antibody, hydrogen peroxide, proteosome bortezomib. In EBV-infected AGS (gastric) cells, knockdown ATM, or inhibits Conversely, treatment these cells nutlin-3 (which ATM) robustly induces p53- ATM-dependent manner. ability R Na dependent. However, overexpression Z presence absence activity. Our results suggest enhances promoter context intact genome effect. Nevertheless, since inhibitors also reduce Burkitt lymphoma have no additional must contribute