An Update on Epstein-Barr Virus and Nasopharyngeal Carcinogenesis

Abstract

Epstein-Barr virus (EBV) is a double stranded DNA cherpesvirus with widespread distribution in all human populations. EBV is associated with a variety of diseases including infectious mononucleosis, hairy leukoplakia, inflammatory pseudotumors, nasopharyngeal carcinoma (NPC), Burkitt’s lymphoma, Hodgkin lymphoma, posttransplant lymphoproliferative disorders, HIV-associated B-cell lymphomas, some T-cell lymphomas particularly extranodal NK/T cell lymphomas of the nasal-type, and a subset of gastric and breast carcinomas. EBV preferentially infects B-lymphocytes through the binding of the major envelop glycoprotein gp350 to the CD21 receptor on the surface of B-cells and through the binding of a second glycoprotein, gp42, to human leukocyte antigen (HLA) class II molecules as a co-receptor [1]. EBV has the capacity to transform resting B-cells into permanent latently infected lymphoblastoid cell lines. Epstein-Barr virus-transformed lymphoblastoid cell lines express a set of viral gene products referred to as latent proteins which include six EBV nuclear antigens (EBNAs 1, 2, 3A, 3B, 3C, -LP) and three latent membrane proteins (LMPs 1, 2A, and 2B). Transformed lymphoblastoid cells also show abundant expression of small, nonpolyadenylated, non-coding RNAs (EBER1 and EBER2) which are expressed in all forms of latent EBV infection. Transcripts from the BamHIA viral genome known as BART-transcripts are also detected in lymphoblastoid cells [2]. EBNA2, EBNA3C and LMP1 are key in the transformation of EBV-infected cells [3, 4]. LMP1 is the main transforming protein of EBV and functions as a classic oncogene in fibroblast transformation assay [5]. LMP1 functions as an activated member of the tumor receptor (TNFR) superfamily, and activates several signaling pathways [6, 7].