Interplay between the Epigenetic Enzyme Lysine (K)-Specific Demethylase 2B and Epstein-Barr Virus Infection

Author:

Vargas-Ayala Romina C.1,Jay Antonin1,Manara Francesca1,Maroui Mohamed Ali23,Hernandez-Vargas Hector4,Diederichs Audrey4,Robitaille Alexis1,Sirand Cecilia1,Ceraolo Maria Grazia15,Romero-Medina Maria Carmen1,Cros Marie Pierre1,Cuenin Cyrille1,Durand Geoffroy1,Le Calvez-Kelm Florence1,Mundo Lucia6,Leoncini Lorenzo6,Manet Evelyne23,Herceg Zdenko1,Gruffat Henri23,Accardi Rosita1

Affiliation:

1. International Agency for Research on Cancer, World Health Organization, Lyon, France

2. CIRI, Centre International de Recherche en Infectiologie (Oncogenic Herpesviruses Team), Université de Lyon, Lyon, France

3. INSERM, U1111, CNRS, UMR5308, ENS de Lyon, Université Claude Bernard Lyon 1, Lyon, France

4. Lyon Cancer Research Center (CRCL), INSERM U1052, Centre Léon Bérard, Lyon, France

5. Tumor Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy

6. Department of Medical Biotechnology, Section of Pathology, University of Siena, Siena, Italy

Abstract

In Africa, Epstein-Barr virus infection is associated with endemic Burkitt lymphoma, a pediatric cancer. The molecular events leading to its development are poorly understood compared with those leading to sporadic Burkitt lymphoma. In a previous study, by analyzing the DNA methylation changes in endemic compared with sporadic Burkitt lymphoma cell lines, we identified several differential methylated genomic positions in the proximity of genes with a potential role in cancer, and among them was the KDM2B gene. KDM2B encodes a histone H3 demethylase already shown to be involved in some hematological disorders. However, whether KDM2B plays a role in the development of Epstein-Barr virus-mediated lymphoma has not been investigated before. In this study, we show that Epstein-Barr virus deregulates KDM2B expression and describe the underlying mechanisms. We also reveal a role of the demethylase in controlling viral and B-cell gene expression, thus highlighting a novel interaction between the virus and the cellular epigenome.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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