Epstein-Barr virus immortalization and latency

Epstein-Barr virus infects human B lymphocytes. The interaction between the virus and these cells has been the subject of investigation for over three decades. Recent in vitro and in vivo studies, reviewed here, are revealing the mechanisms by which EBV induces and controls proliferation through the expression of six viral nuclear proteins and two plasma membrane proteins. This genetic program is referred to as immortalization and it is suggested that the purpose of immortalization is to use the innate proliferative potential of B cells to inflate the numbers of infected cells prior to virus production and cell lysis. Latency, on the other hand, has only been detected in situ in latently infected humans. It is characterized by the presence of very low numbers of viral episomes that appear to express the RNA for only one protein (Latent Membrane Protein 2) in B cells that bear the markers of a non-activated resting memory subset. Two models are proposed for the mechanism that establishes this state. The differences between immortalization and latency are highlighted in this review and it is suggested that many of the functions currently attributed to latency are actually features of immortalization. An appreciation of this distinction may assist the discussion of the nature of the interaction between the virus and the host in EBV-associated lymphoproliferative diseases and tumors.