The nucleotide polymorphisms within the Epstein–Barr virus C and Q promoters from nasopharyngeal carcinoma affect transcriptional activity in vitro

Abstract

Epstein-Barr virus (EBV) is a ubiquitous human gamma herpesvirus that is associated with Burkitt's lymphoma (BL), gastric carcinoma, nasopharyngeal carcinoma (NPC), and NK/T-cell lymphoma. Two viral promoters, Cp and Qp, are important for EBV latent infection. The latency Cp, which is used in primary infection, drives expression of the full spectrum of EBV nuclear antigens. Qp is active in EBV-associated tumors and drives the latency I/II expression pattern. In this study, we determined nucleotides polymorphisms in the Cp and Qp promoter regions in peripheral blood mononuclear cells (PBMCs) from Cantonese healthy carriers and in biopsies of NPC, nasal NK/T lymphoma, BL, and gastric carcinoma. The sequence changes of -12G>T and +69 C>T in Cp and -197 G>A and +1 G>C in Qp were frequently identified in NPC. Transient transfection studies using luciferase gene reporters revealed a significant reduction (57.11%) in gene expression from the Cp +69T variant and increased expression (43.5%) from the Qp +1C variant compared to the prototype, suggesting that these sequence variations affect promoter activity. Our results indicate that the nucleotides polymorphisms in Cp and Qp occur frequently in NPC and might contribute to the oncogenesis of EBV.