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

TLDR

Human herpesvirus‑8 is implicated in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma, yet its universal presence in early Kaposi’s sarcoma lesions has not been demonstrated. The study aimed to map the distribution of HHV‑8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. This mapping was performed using the LN53 monoclonal antibody against latent nuclear antigen‑1 encoded by ORF73. HHV‑8 was found in less than 10 % of vessel‑wall cells in early Kaposi’s sarcoma, in over 90 % of spindle cells and perivascular cells in nodular Kaposi’s sarcoma (but not in normal endothelium), colocalized with VEGFR‑3, and was more abundant in VEGFR‑3‑positive endothelium than in LNA‑1‑positive cells; in multicentric Castleman’s disease it was confined to mantle‑zone immunoblastic B cells, while no LNA‑1 staining was observed in multiple myeloma, prostate cancer, or angiosarcoma, indicating no etiologic link.

Abstract

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and 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 endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.