Stable expression of Epstein-Barr virus BZLF-1-encoded ZEBRA protein activates p53-dependent transcription in human Jurkat T-lymphoblastoid cells

Interaction between viral proteins and tumor suppressor p53 is a common mec hanism of viral pathogenesis. The Epstein-Barr virus (EBV) BZLF-1 ORF-encod ed ZEBRA protein (also denoted EB1, Z, Zta) binds to p53 in vitro and has b een associated with the altered transcription of p53-regulated genes in B l ymphocytes and epithelial cells. In this work, jurkat T-lymphoblastoid cell s that express ZEBRA were characterized by the use of transiently transfect ed p53 and p53 reporter genes. Stable expression of ZEBRA was associated wi th the activation of p53-dependent transcription and increased p53 dependen t apoptotic cell death. In Jurkat cell lines, stably expressed ZEBRA protei n was apparently localized to the cell cytoplasm, in contrast to the typica l nuclear localization of this protein in other cell types. Previous studie s have suggested that EBV infection of T lymphocytes may contribute to the malignant transformation of T cells and the increased replication of human immunodeficiency virus. Our observations suggest a mechanism through which ZEBRA protein expressed in human T lymphocytes could alter T-cell prolifera tion and apoptosis during EBV infection. (C) 2000 by The American Society o f Hematology.