Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease

Human herpesvirus 8 (HHV-8) infection has been implicated in the etiology o f Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), three diseases that frequently develop in immuno compromised, human immunodeficiency virus-positive individuals. One hypothe sis that would account for different pathological manifestations of infecti on by the same virus is that viral genes are differentially expressed in he terogeneous cell types. To test this hypothesis, we analyzed the localizati on and levels of expression of two viral genes expressed in latent and lyti c infections and the viral homologue of interleukin-6 (vIL-6). We show that PEL parallels KS in the pattern of latent and lytic cycle viral gene expre ssion but that the predominant infected cell type is a B cell. We also show that IMCD differs from KS not only in the infected cell type (B-cell and T -cell lineage) but also in the pattern of viral gene expression. Only a few cells in the lesion are infected and all of these cells express lytic-cycl e genes. Of possibly greater significance is the fact that in a comparison of KS, PEL, and MCD, we found dramatic differences in the levels of express ion of vIL-6. Interleukin-6 is a B-cell growth and differentiation factor w hose altered expression has been linked to plasma cell abnormalities, as we ll as myeloid and lymphoid malignancies. Our findings support the hypothesi s that HHV-8 plays an important role in the pathogenesis of PEL and MCD, in which vIL-6 acts as an autocrine or paracrine factor in the lymphoprolifer ative processes common to both.