The Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein required for Blymphocyte immortalization, induces the synthesis of type I interferon in Burkitt's lymphoma cell lines

Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein involved in cell tr ansformation, interferes with the cellular response to type I interferons ( IFN-alpha/beta). We investigated the function of conditionally expressed EB NA2 in the context of the IFN response in Burkitt's lymphoma cell lines, Ex pression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes (ISGs), genes which contain within thei r promoters either the interferon-stimulated response element (ISRE) or the gamma interferon activation site (GAS). In search of a molecular mechanism for the transcriptional induction of ISGs, we observed an EBNA2-dependent synthesis of IFN-beta mRNA at low levels and the secretion of low amounts o f IFN. A transfected IFN-beta promoter responded to EBNA2 activation, and a sequence closely resembling a RBP-J kappa binding site was pinpointed as a potential target of EBNA2 activity, EBNA2-dependent transcriptional induct ion of the IFN-beta promoter occurred in EBV-negative Burkitt's lymphoma ce lls, indicating that other EBV genes were not required for the induction of IFN-beta synthesis.