IntechOpen Book Series Infectious Diseases Volume 11

Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet's research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses' effects on humans (both their impact on pathology and their symbiotic relationships in

humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online *Encyclopedia of Environment* and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.

**Editor of Volume 11: Emmanuel Drouet** Institut de Biologie Structurale (Complement, antibodies and infectious diseases group) Université de Grenoble-Alpes, Grenoble, France

**Book Series Editor: Shailendra K. Saxena** King George's Medical University

## Scope of the Series

Contents

from EBV-Related Malignancies

*by Sylvie Ranger-Rogez*

with New Relevance

*by Andi Arus Victor*

on Predictive Tests? *by Emmanuel Drouet*

*and Mafalda Basílio Timóteo*

*Renato Mantegazza and Pia Bernasconi*

*by Ying Liu, Zheming Lu and Hongying Huang*

EBV Genome Mutations and Malignant Proliferations

Epstein-Barr Virus-Associated Gastric Cancer: Old Entity

*by Hugo Manuel Lopes de Sousa, Joana Patrícia Costa Ribeiro* 

Epstein-Barr Virus in Myasthenia Gravis: Key Contributing Factor Linking Innate Immunity with B-Cell-Mediated Autoimmunity *by Federica Bortone, Letizia Scandiffio, Paola Cavalcante,* 

Epstein-Barr Virus: Should We Still Invest in Vaccines or Focus

Ocular Manifestations in Epstein Barr Virus Infection

**Preface XI**

**Chapter 1 1**

**Chapter 2 19**

**Chapter 3 45**

**Chapter 4 67**

**Chapter 5 75**

**Chapter 6 97**

Genome-Wide Profiling of Epstein-Barr Virus (EBV) Isolated

The series will give a most comprehensive overview of recent trends in various infectious diseases (as per the most recent Baltimore classification), as well as general concepts of infections, immunopathology, diagnosis, treatment, epidemiology and etiology to current clinical recommendations in management of infectious diseases, highlighting the ongoing issues, recent advances, with future directions in diagnostic approaches and therapeutic strategies. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is very important for safeguarding human race from more loss of resources and economies due to pathogens.

## Contents


Preface

Epstein-Barr virus (EBV) is one of the most common human viruses and the cause of pathologies such as infectious mononucleosis (IM) and certain cancers, namely immunodeficiency-related B cell lymphomas, Burkitt and Hodgkin, nasopharyngeal, and gastric carcinomas. Over the past two decades, the possibility of an association between EBV and other cancers and other chronic pathologies (i.e., multiple sclerosis (MS)) has also been put forward. One of the challenges facing researchers is the complicated life cycle of EBV, which goes through a phase of latent infection during which the virus induces the activation, proliferation, and differentiation of primary B cells into memory B cells. Additionally, EBV, like other human herpesviruses (HHV1-8), has co-evolved through a persistent viral infection in the host, and is then spread efficiently to others, generally without causing serious diseases. Symptoms of EBV infection vary widely based on the age and immune status of the patient. Most infections in younger children are benign and are often subclinical. EBV is also associated with autoimmune diseases, including rheumatoid arthritis, Sjogren's

Classified as a herpesvirus (type IV), EBV encodes more than 80 genes. The core set of genes (minority) are involved in the latency phase. The other set comprises the genes of the lytic cycle. In addition to these gene-encoding proteins, there are gene-encoding microRNAs (regulatory RNAs), the functions of which are still poorly understood. For many years, researchers argued that only the products of the latency genes (i.e., LMP1 oncoprotein and EBNAs) were responsible for oncogenesis. It has recently been demonstrated that the proteins of the lytic cycle have also a role not only in cell transformation (the initial stage of the tumor process) but also in tumor progression. Certain viral proteins act as "transcription factors" capable of activating cellular genes involved in the regulation of cell

EBV-associated lymphomas are classically described as malignant proliferations of the lymphoid type but nonetheless group together a wide variety of histological and immunological types. In addition, this association with EBV, considered to be a group 1 carcinogen according to the International Agency for Research on Cancer (IARC) 2009, is highly variable for the type of lymphoma considered. For example, in Burkitt's lymphoma (BL), which was the first cancer associated with an infection and observed in Ugandan children thanks to the work of Denis Burkitt in 1958, we find it is the B lymphoma associated with EBV (discovered eight years later) that is present in more than 90% of cases. In contrast, in the same type of lymphoma but observed in a European subject, the association is only around 20%. This demonstrates that, in addition to the virus, there are environmental co-factors linked to each form of lymphoma, (regardless of whether it is type B or type T) or even a specific lymphoma, such as lymphoma by Hodgkin. The immune state is one of these cofactors linked to the host, and this explains the appearance of severe lymphoproliferative diseases in immunocompromised subjects (e.g., transplant recipients). In these patients, these lymphomas are called post-transplantation lymphoproliferative syndromes (PTLDs), bringing together several types of lymphomas (B lymphomas most often associated

with EBV, but also T lymphomas, BLs, or Hodgkin's disease).

syndrome, systemic lupus erythematosus, and MS.

survival or even in immunomodulation.
