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.
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.
Brousset
P
P
Laboratoire d'Anatomie Pathologique, Centre Hospitalier Universitaire de Purpan, Toulouse, France.
Cesarman
E
E
Meggetto
F
F
Lamant
L
L
Delsol
G
G
D017209:Apoptosis; D005871:Castleman Disease / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis*; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology / Q000821:virology; D009687:Nuclear Proteins / Q000032:analysis*; D010750:Phosphoproteins; D016133:Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology* / Q000821:virology
D004279:DNA, Viral; D015850:Interleukin-6; D009687:Nuclear Proteins; D010750:Phosphoproteins; C118485:latent nuclear antigen (LNA)