Section 5 Epstein-Barr Virus

**97**

**Chapter 6**

Therapy

**Abstract**

lymphoma

**1. Introduction**

*Emmanuel Drouet*

The Role of the Epstein-Barr Virus

Lytic Cycle in Tumor Progression:

The Epstein-Barr virus (EBV) reactivation corresponds to the activation of EBV global replication involving not only the origin of the latent viral replication but also that of the origin of lytic replication. During this reactivation, a minority of B cells infected with EBV in its latent form enter the lytic phase. During this phase, all EBV proteins are produced, enabling the assembly of complete virions that lysate their host cells and infect neighboring cells (lytic cycle). This horizontal EBV transmission seeks to increase the pool of EBV-infected B cells. This chapter seeks to review the role of the lytic EBV proteins (particularly that of the ZEBRA protein) *in tumor development*. This protein is the main transcription factor of EBV, expressed during the activation of the lytic cycle. Recently, we demonstrated that this immediate early protein can be detected in the soluble state (s-ZEBRA) in the serum of patients with posttransplant lymphoproliferative disorder. We highlighted the role of ZEBRA in EBV pathogenesis in transplanted subjects, not only as a key protein in the activation of EBV replication but also as a protein "toxoid" released into the extracellular milieu. This release could result in increased secretion of immunomodulatory cytokines and that of angiogenesis-promoting factors conducive to tumor progression.

**Keywords:** tumor progression, tumorigenesis, EBV, lytic cycle, Zta/ZEBRA protein,

Epstein-Barr virus (EBV) is a member of the herpesvirus family and only infects primates, with tropism for B cells and epithelial cells, which establishes a lifelong persistent infection in over 90% of the world's population [1]. After the resolution of the primary infection episode, EBV enters a latent phase. Following primary infection, the virus establishes lifelong persistence within the host memory B-cell compartment utilizing restricted latent gene expression programs [2–4]. Like all herpesviruses, EBV can choose between two alternative lifestyles: latent or lytic replication. EBV lytic replication, which is required for horizontal spread of the virus from cell to cell, and from host to host, occurs in both epithelial cells and B cells [5–7]. During latency, EBV exists in a dormant state where only a viral gene subset is expressed, facilitating the episomal persistence of the viral genome [8]. However,

Consequences in Diagnosis and
