Inactivation of NF-kappa B by EBV BZLF-1-encoded ZEBRA protein in human T cells

We have previously shown that the EBV ZEBRA protein (also denoted EB1, Z, o r Zta) encoded by the BZLF open reading frame is expressed in primary human thymocytes and in human T lymphoblastoid cell lines infected by EBV, Expre ssion of EBV-encoded gene products in T lymphocytes could contribute to vir al pathogenesis during acute EBV infection as well as in individuals coinfe cted with EBV and HIV. HPB-ALL and Jurkat T lymphoblastoid cell lines trans iently and stably expressing ZEBRA were characterized in this work. Express ion of ZEBRA protein in human T lymphoblastoid cells was associated with de creased expression of an NF-kappa B reporter gene, altered expression of th e NF-kappa B p50 protein subunit, and decreased DNA binding by components o f NF-kappa B, These observations suggest that inactivation of NF-kappa B tr anscription by ZEBRA in EBV-infected T cells may be a novel mechanism of vi ral pathogenesis analogous in part to over-expression of the endogenous cyt oplasmic inhibitor of NF-kappa B, I kappa B alpha.