Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogen esis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early K S has not yet been shown. We used a mAb (LN53) against latent nuclear antig en-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cel l types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, a nd PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit -like vessels and in >90% of spindle cells, but not in normal vascular endo thelium. In addition, HHV-8 colocalizes with vascular endothelial growth fa ctor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-I, ind icating that HHV-8 is not inducing the proliferation of VEGFR-3-positive en dothelium directly. In MCD, HHV-8 is present in mantle zone large immunobla stic B cells. No staining for LNA-1 is seen in samples from multiple myelom a, prostate cancer, and angiosarcoma, supporting the absence of any etiolog ical link between these diseases and HHV-8.