KSHV/HHV8-associated lymphoproliferations in the AIDS setting

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is associated with two lymphoproliferative disorders in the AIDS setting, primary effusion lymphoma (PEL) and the plasma cell variant of multicentric Castleman's disease (MCD). In PEL, KSHV persists in a latent form in most lymphoma cells, although viral production has been seen infrequently. In MCD, the viral gene expression pattern is less restrictive, virus production appears to occur and to correlate with the severity of this disease. Several viral genes may contribute to the particular features of these two disorders: among them a viral homologue of interleukin 6 (vIL6) has attracted much attention and been shown to promote the growth of plasma cells. It is thought that its activity is important in the pathogenesis of both PEL and MCD. Other viral genes, in particular a D-type cyclin homologue, the latent nuclear antigen LANA, and one or more of the viral homologues of interferon regulatory factors (vIRFs) may also contribute. Although it is conceivable that viral infection per se could explain much, if not all, of the features of MCD, it is likely that additional genetic alterations play a role in the pathogenesis of PEL.