Epstein-Barr virus latency: current and future perspectives

Abstract

EBV drives resting B cells to continuous proliferating latently infected cells. A restricted program of viral transcription contributes to latency and cell proliferation important for growth transformation. Recent interest in latency and transformation has provided new data about the roles of the EBV encoded latent proteins and non-coding RNAs. We broadly describe the transcription, epigenetic, signaling and super-enhancer functions of the latent nuclear antigens in regulating cellular transcription; the role of LMP2 in utilization of the autophagosome to control cell death, and the association between LMP1, the linear ubiquitin chain assembly complex and TRAF1 which are important for transformation. This review explores recent discoveries with new insights into therapeutic avenues for EBV related malignancies.

Figure 1

The schematic shows a comprehensive view of the many components of the latent life cycle of EBV involving the latent membrane proteins (LMPs) and nuclear antigens (EBNAs) as well as the small RNAs encoded by EBV. EBV infection of resting B-lymphocytes lead to expression of the complete set of latent transcripts. The LMPs are involved in dysregulating a number of number of major cellular pathways including JNK, PI3K and NF-KB as well as reactivation of the virus. The small RNAs are now shown to be involved in a number of different activities including replication and apoptosis. EBNAs target a wide range of cellular processes from gene expression, genome maintenance, tumor suppression and cell cycle regulation. These activities contribute the EBV mediated B-lymphocyte transformation of infected cells and suggest that a coordinated set of these activities are critical for driving the linked pathologies.