Abstract 2392: The role of ATM in lytic infection of EBV in nasopharyngeal epithelial cells

Abstract

Abstract Epstein-Barr virus (EBV), a type of oncogenic herpesvirus, is associated with human malignancies. Previous studies have shown that reactivation of EBV in infected cells induces ATM-dependent DNA damage response (DDR). The functional role and involvement of ATM activation during lytic induction remains obscure. In this study, the essential role of ATM for viral DNA replication was examined in EBV-infected nasopharyngeal epithelial cells. Induction of lytic EBV infection triggers ATM activation and localization of DDR proteins at the viral replication compartments. Suppression of ATM activity using siRNA approach or specific chemical inhibitor diminished EBV DNA replication and production of infectious virion in EBV-infected cells induced to undergo lytic infection. Phosphorylation of Sp1 is a downstream event of ATM activation. The phosphorylation of Sp1 at serine 101 residue is crucial in promoting the accretion of EBV replication proteins at the replication compartment to facilitate viral DNA replication. Depletion of Sp1 suppresses viral DNA replication and localization of EBV replication proteins to the replication compartments. Our studies support an important role of ATM activation in lytic infection of EBV. Phosphorylation of Sp1 is an essential process mediating the recruitment of EBV replication protein to replication compartments. Our study highlights the importance of DDR pathway in lytic infection of EBV and suggests the potential application of specific DDR inhibitors to control the EBV replication in infected cells. Funding support: Research Grant Council of Hong Kong (GRF #779312 & 779713; AoE/M-06/08). Note: This abstract was not presented at the meeting. Citation Format: George Sai-Wah Tsao, Pok Man Hau. The role of ATM in lytic infection of EBV in nasopharyngeal epithelial cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2392. doi:10.1158/1538-7445.AM2014-2392