Rhadinoviruses: KSHV and Associated Malignancies

Abstract

Kaposi’s Sarcoma Herpesvirus (KSHV), discovered in 1994, is the only known Rhadinovirus (γ2-herpesvirus) to naturally infect humans. In addition to Kaposi’s Sarcoma (KS), one of the most common HIV-associated malignancies, KSHV is strongly associated with two rare lymphoproliferative disorders, namely, primary effusion lymphoma (PEL) and the plasmablastic variant of multicentric Castleman’s disease (MCD). Epidemiological arguments strongly link KSHV to KS and KSHV is found in endothelial spindle cells, the neoplastic component of KS. This tumour appears to be the result of an oligo/polyclonal expansion of atypically differentiated, but not fully transformed, endothelial cells accompanied by pronounced inflammatory and angiogenic features. The plasma cells variant of MCD is characterised by a proliferation of monotypic, KSHV-infected B-cell population with plasmablastic features. By contrast, PEL represents a monoclonal, fully transformed, malignant B-cell proliferation with the survival of PEL cells, depending on the presence of latent KSHV proteins. Co-factors such as immunosuppression, and perhaps also immune activation, play an important role in KSHV-induced oncogenesis.