KSHV/HHV8-associated lymphoproliferations in the AIDS setting

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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.

Section snippets

Association of KSHV/HHV8 with lymphoproliferative disorders in AIDS patients

Kaposi's sarcoma-associated herpesvirus (KSHV) [111] or human herpesvirus 8 (HHV8) is consistently associated with two lymphoproliferative conditions often seen in AIDS patients. It is found in nearly all cases of ‘body cavity-based’ or ‘primary effusion lymphoma’ (BCBL/PEL) and it has been proposed that the presence of HHV8 DNA is a defining feature of this condition. It is also associated with the plasmacytic form of Multicentric Castleman's Disease (MCD), and is found in most cases of MCD in

Phenotypic and molecular characteristics

Primary effusion lymphoma (PEL), also called body cavity-based lymphoma (BCBL), is a rare lymphoma in AIDS patients characterised by its presentation as a malignant effusion in the peritoneal, pleural or pericardial space, most often in the absence of an obvious tumour mass. The lymphoma cells have pleomorphic or anaplastic features combining morphological aspects of large cell immunoblastic and anaplastic large cell lymphomas [6]. They display marked size heterogeneity, irregular and

Multicentric Castleman's disease

Castleman's disease is a localised lymphoproliferative condition, often found in the mediastinum, mesenterial or peripheral lymph nodes and characterised histologically by expanded germinal centres with B cell proliferation and vascular proliferation. Two histological types have been recognised: one, characterised by a pronounced plasma cell proliferation and persistence of the nodal architecture (‘plasma cell variant’), and the other by abnormal germinal centres and abundant hyalinised vessels

Biological and biochemical properties of KSHV viral genes expressed in KSHV-associated lymphoid malignancies in AIDS patients

As reviewed elsewhere 79, 80, several KSHV genes have been implicated in pathogenesis. A comprehensive discussion of their properties would go beyond the scope of this review, and for many of them their expression in lymphoid malignancies is not clear. The following overview is therefore confined to those viral proteins that have been documented to be expressed in PEL or MCD tissues.

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