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

Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4546-51. doi: 10.1073/pnas.96.8.4546.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Biomarkers / analysis
  • Bone Marrow / pathology
  • Bone Marrow / virology
  • Castleman Disease / pathology
  • Castleman Disease / virology*
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / virology
  • Herpesvirus 8, Human / isolation & purification*
  • Herpesvirus 8, Human / physiology*
  • Humans
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Lymphoma / pathology
  • Lymphoma / virology*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / virology
  • Polymerase Chain Reaction
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptors, Cell Surface / analysis
  • Sarcoma, Kaposi / pathology
  • Sarcoma, Kaposi / virology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Vascular Endothelial Growth Factor Receptor-3
  • Virus Latency*

Substances

  • Antigens, CD
  • Biomarkers
  • Receptors, Cell Surface
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-3