How Epstein Barr Virus Causes Lymphomas

Abstract

Since Epstein-Barr Virus (EBV) was isolated 60 years ago, it has been studied clinically, epidemiologically, immunologically, and molecularly in the ensuing years. These combined studies allow a broad mechanistic understanding of how this ubiquitous human pathogen which infects more than 90% of adults can rarely cause multiple types of lymphomas. We survey these findings to provide a coherent description of its oncogenesis.

Keywords: EBV; lymphomas.

Figure 1

Depicted are possible relationships between cells expressing different sets of EBV genes and the types of lymphomas found to express these subsets. Many of the assays for EBV gene expression also come from analyzing cells grown in vitro so that the subsets of genes expressed in vivo are not certain. The arrows represent possible progressions of cells that express one subset of viral genes to ones that express another subset. How each of these cell types evolves to be a bona fide lymphoma must be complex and uncertain. Upon the infection of naïve B cells, EBV expresses all latent genes (Latency III) which appear eventually to be restricted in expression along the path of B cell differentiation, which includes the germinal center reaction. Ultimately, EBV persists in recirculating memory B cells and expresses no detected viral proteins (Latency 0). Latent EBV may be activated by immunosuppression, chronic immune activation, or mutations, and can begin expressing viral proteins (Latency II and III), leading to B cells proliferating and potentially to lymphomagenesis.