Colocalization of the viral interleukin-6 with latent nuclear antigen-1 of human herpesvirus-8 in endothelial spindle cells of Kaposi's sarcoma and lymphoid cells of multicentric Castleman's disease

Hum Pathol. 2001 Jan;32(1):95-100. doi: 10.1053/hupa.2001.21131.


Human herpesvirus-8 (HHV-8) also called Kaposi's sarcoma-associated herpesvirus infects spindle cells in Kaposi's sarcoma (KS) and lymphoid cells in multicentric Castleman's disease (MCD). In KS cells, HHV-8 is mainly latent with the expression of latent nuclear antigen-1 (LNA-1), whereas in MCD both lytic and latent antigens are produced by lymphoid cells. We show by immunohistochemical labeling that in KS viral interleukin-6 (vIL-6) is expressed in rare spindle cells, whereas in MCD, vIL-6 is detectable in lymphoid cells around lymphoid follicles but also within the follicular dendritic reticulum cell network. The staining of apoptotic bodies with anti IL-6 antibody suggests the achievement of a complete lytic cycle in a subset of lymphoid cells. Interestingly, in MCD, some areas contained vascular spindle cells latently infected by HHV-8 on the basis of LNA-1 expression. This finding might imply that in MCD, both vascular and lymphoid cells proliferate in response to the viral infection. Double immunostaining with anti LNA-1 and anti vIL-6 in MCD and KS identifies 2 subsets of HHV-8 infected (vascular and lymphoid) cells, some with exclusive expression of LNA-1 and some with coexpression of vIL-6 and LNA-1. This suggests that in vivo the regulation of the expression vIL-6 and LNA-1 protein varies with the cell type. In addition, the detection of infected endothelial cells in MCD may indicate that these cells belong to the reservoir for HHV-8.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis
  • Castleman Disease / metabolism
  • Castleman Disease / pathology*
  • Castleman Disease / virology
  • DNA, Viral / genetics
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / virology
  • Herpesvirus 8, Human* / chemistry
  • Herpesvirus 8, Human* / genetics
  • Humans
  • Immunohistochemistry
  • Interleukin-6 / analysis*
  • Lymphocytes / chemistry
  • Lymphocytes / pathology
  • Lymphocytes / virology
  • Nuclear Proteins / analysis*
  • Phosphoproteins*
  • Polymerase Chain Reaction
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / pathology*
  • Sarcoma, Kaposi / virology


  • DNA, Viral
  • Interleukin-6
  • Nuclear Proteins
  • Phosphoproteins
  • latent nuclear antigen (LNA)