Epstein–Barr virus proteins involved in cell immortalization

Abstract

Abstract The discovery in 1964 of herpesvirus particles in tumour cell lines derived from patients with Burkitt’s lymphoma (1) was a crucial observation that subsequently led to the so-called Epstein-Barr virus (EBY) being the first virus to be implicated in the pathogenesis of a human cancer. This gammaherpesvirus has since been associated with several other malignant diseases, including nasopharyngeal carcinoma, B cell lymphomas in immunosuppressed patients, certain T cell lymphomas, and Hodgkin’s disease (2). Absolute proof of the involvement of EBY in these malignancies was hampered by the unexpected finding that EBY was in fact a ubiquitous virus, being carried as a persistent and largely asymptomatic infection by more than 95% of adults in all populations world-wide (2). However, in support of its potential oncogenic properties, EBY was found to be a powerful transforming agent for normal resting human B lymphocytes in vitro, resulting in the regular outgrowth of EBY-immortalized lymphoblastoid cell lines (LCL) (3). Viral gene expression in LCL is restricted to about nine of the approximately 100 genes encoded by EBY and, since LCL are largely non-permissive for virus production, the EBY genes expressed in LCL were defined as latent genes. Six of the latent genes encode the nuclear antigens, EBNA-1,- 2, -3A,-3B, -3C., and -LP, while three encode the latent membrane proteins, LMP-1, -2A, and -2B; the most abundantly expressed latent transcripts in LCL are non-polyadenylated RNA, the EBERs, that do not encode proteins.