Gammaherpesvirus and lymphoproliferative disorders in immunocompromised patients

Abstract

Two lymphotropic human gamma herpesviruses can cause lymphoproliferative disorders: Epstein Barr virus (EBV, formally designated as human herpesvirus 4) and Kaposi sarcoma herpesvirus (KSHV, also called human herpesvirus 8). Individuals with inherited or acquired immunodeficiency have a greatly increased risk of developing a malignancy caused by one of these two viruses. Specific types of lymphoproliferations, including malignant lymphomas, occur in individuals with HIV infection, transplant recipients and children with primary immunodeficiency. Some of these diseases, such as Hodgkin's and non-Hodgkin lymphoma resemble those occurring in immunocompetent patients, but the proportion of tumors in which EBV is present is increased. Others, like primary effusion lymphoma and polymorphic post-transplant lymphoproliferative disorder are rarely seen outside the context of a specific immunodeficient state. Understanding the specific viral associations in selected lymphoproliferative disorders, and the insights into the molecular mechanisms of viral oncogenesis, will lead to better treatments for these frequently devastating diseases.

Figure 1. Infection with EBV or KSHV in malignancies occurring in patients with immunodeficiency

The major subtypes of lymphoproliferative are shown in boxes, with arrows indicating the cause of immunodeficiency and the most common associations. Percentage of EBV infection is an approximation based on a compilation of the literature and the author’s personal experience, and reflects only the proportion of cases in the context of HIV infection; these numbers are much lower for MCD, DLBCL and HL in individuals without overt immunodeficiencies. Abbreviations: MCD: Multicentric Castleman’s disease, PH: plasmacytic hyperplasia, PBCH: polymphrphic B cell hyperplasia, PEL: primary effusion lymphoma, BL: Burkitt lymphoma, PBL: plasmablastic lymphoma, DLBCL: Diffuse large B cell lymphoma.

Figure 2. Major patterns of EBV and KSHV latent gene expression in lymphoproliferative disorders

The main EBV latency patterns and the most common lymphoproliferative disorders in which these patterns are seen are illustrated. The KSHV proteins that are uniformly expressed in PEL and MDC are shown in the right.