Transcription of the Epstein-Barr virus gene EBNA-1 from different promoters in nasopharyngeal carcinoma and B-lymphoblastoid cells

Abstract

Transcriptional expression of the Epstein-Barr virus (EBV) genome has been shown to differ markedly between nasopharyngeal carcinoma (NPC) cells and latent B-cell lines, with a more limited pattern of gene expression seen in NPC. EBNA-1 is the only nuclear antigen so far detected in both NPC and Burkitt's lymphoma cells. We found previously that in a human NPC tumor passaged in nude mice, designated C15, the EBNA-1 mRNA contained a novel splice site in the BamHI Q region of EBV which had not previously been described for B-cell lines. This lies within a region of the EBV genome to which EBNA-1 binds. Here, we further characterize the 5' region of EBNA-1 transcripts and identify two splicing patterns in C15 cells; we show that they are derived from a common promoter region in the BamHI F region of the viral genome. We also demonstrate that this region can function to initiate transcription of the chloramphenicol acetyltransferase gene in epithelial cells and that the promoter region is only partially methylated at CpG sites in the tumor. In contrast, a B-lymphoblastoid cell line derived from C15 uses a conventional promoter in BamHI-C/W for expression of EBNA-1.