The tumor suppressor gene p53 plays a central role in the maintenance of normal cell growth and genetic integrity, while its impact on the Epstein-Barr virus (EBV) life cycle remains elusive. We found that p53 is important for histone deacetylase inhibitor-induced EBV lytic gene expression in nasopharyngeal carcinoma cells. Restoration of p53 in p53-null, EBV-infected H1299 cells augments the potential for viral lytic cycle initiation. Evidence from reporter assays demonstrated that p53 contributes to the expression of the immediate-early viral Zta gene. Further analysis indicated that the DNA-binding ability of p53 and phosphorylation of Ser392 may be critical. This study provides the first evidence that p53 is involved in the regulation of EBV lytic cycle initiation.
