How Epstein-Barr Virus “Manipulates” The Tumoral Microenvironment in Hodgkin Lymphoma?

Abstract

Abstract The Epstein-Barr virus (EBV) is a gamma-herpesvirus that colonizes the B-cell system of its human host, allowing it to persist asymptomatically in the majority of the world’s adult population. In most people primary infection goes unnoticed, whereas in a minority of individuals, primary infection results in infectious mononucleosis (IM), a benign condition that almost always resolves after several weeks or months. However, EBV is also causally linked with a number of malignancies, including B-cell lymphomas, such as classical Hodgkin lymphoma (cHL). A proportion of patients with cHL harbor EBV within their tumor cells. Emerging evidence suggests that while EBV is able to subvert cellular processes to promote the growth and survival of HRS cells or their progenitors, mutations in key cell signalization pathways are probably required to do this when EBV is absent. The challenge is to unravel exactly how EBV and its latent genes contribute to the pathogenesis of cHL particularly with respect to how the virus co-operates with cellular genetic and epigenetic changes to drive transformation. It is hoped that the development of better in vitro and in vivo models of disease will reveal more fundamental aspects of EBV’s role in Hodgkin lymphoma pathogenesis and pave the way for targeted therapies for patients with EBV-positive cHL.