The contribution of ebv to the pathogenesis of classical hodgkin  lymphoma

Hodgkin lymphoma (HL) exists in two major forms, the so-called classical type (cHL) and the nodular lymphocyte predominant type (NLPHL). Since NLPHL is considered to be an EBV-negative entity, this review focusses only on the cHL form. Although cHL is a curable disease in many cases, we still lack an understanding of its pathogenesis that could lead to kinder treatments for patients, and also to more effective therapies for the smaller subset of patients who are destined to die of their disease. One approach might be to therapeutically target the Epstein-Barr virus (EBV), which is present in up to one-half of cases in resource rich nations, and in almost all cases in some resource-poor countries. However, it has been suggested that EBV might be simply a silent passenger in cHL. In this review, we present evidence in support of a crucial role for EBV in virus-positive cHL. In particular, we highlight important epidemiological differences between EBV-positive and EBV-negative cHL that suggest different aetiologies, as well as genetic differences, including a different profile of somatic mutations pointing to a distinct contribution for EBV in substituting for cellular genetic changes that are required for disease development when the virus is absent. We also focus attention on important roles for the individual latent virus genes in the pathogenesis of cHL. Overall, this review suggests that a better understanding of how EBV contributes to the pathogenesis of cHL may eventually lead to improved stratification of patients and to the development of therapies that specifically target EBV or its latent genes.