CD68⁺cells of monocyte/macrophage lineage in the environment of AIDS-associated and classic-sporadic Kaposi sarcoma are singly or doubly infected with human herpesviruses 7 and 6B

Abstract

Earlier studies have shown that Kaposi sarcomas contain cells infected with human herpesvirus (HHV) 6B, and in current studies we report that both AIDSassociated and classic-sporadic Kaposi sarcoma contain HHV-7 genome sequences detectable by PCR. To determine the distribution of HHV-7-infected cells relative to those infected with HHV-6, sections from paraffin-embedded tissues were allowed to react with antibodies to HHV-7 virion tegument phosphoprotein pp85 and to HHV-6B protein p101. The antibodies are specific for HHV-7 and HHV-6B, respectively, and they retained reactivity for antigens contained in formalin-fixed, paraffin-embedded tissue samples. We report that (i) HHV-7 pp85 was present in 9 of 32 AIDS-associated Kaposi sarcomas, and in 1 of 7 classical-sporadic HIV-negative Kaposi sarcomas; (ii) HHV-7 pp85 was detected primarily in cells bearing the CD68 marker characteristic of the monocyte͞ macrophage lineage present in or surrounding the Kaposi sarcoma lesions; and (iii) in a number of Kaposi sarcoma specimens, tumor-associated CD68 ؉ monocytes͞macro-phages expressed simultaneously antigens from both HHV-7 and HHV-6B, and therefore appeared to be doubly infected with the two viruses. CD68 ؉ monocytes͞macrophages infected with HHV-7 were readily detectable in Kaposi sarcoma, but virtually absent from other normal or pathological tissues that harbor macrophages. Because all of the available data indicate that HHV-7 infects CD4 ؉ T lymphocytes, these results suggest that the environment of the Kaposi sarcoma (i) attracts circulating peripheral lymphocytes and monocytes, triggers the replication of latent viruses, and thereby increases the local concentration of viruses, (ii) renders CD68 ؉ monocytes͞macrophages susceptible to infection with HHV-7, and (iii) the combination of both events enables double infections of cells with both HHV-6B and HHV-7.

Anatomical mapping of human herpesvirus reservoirs of infection

“…Virus has been obtained from peripheral blood T cells and monocytes, saliva, salivary glands, and uterine cervical secretions. 49,50 HHV-7 DNA has been detected in saliva and salivary gland epithelium from healthy adults. 45,51 By immunohistochemistry, HHV-7 antigen has been detected in lymph node, tonsils, liver, and kidney of healthy adults.…”

RANTES Binding and Down-Regulation by a Novel Human Herpesvirus-6 β Chemokine Receptor

“…We also show U51 can bind HHV-8 vMIPII. This binding is of interest, as HHV-6 has been identified in HHV-8-associated Kaposi sarcoma lesions, and chemotaxis of HHV-6-infected cells chemoattracted via U51 specificity for vMIPII could affect migration of HHV-6-infected cells to an HHV-8-associated lesion, possibly affecting pathology (41). Additionally, we have shown that U51 has some specificity for eotaxin, like CCR3, but also to MCP-3 and MCP-4, thus displaying a binding profile to a subset of CC chemokines that is distinct from those of receptors described to date.…”

Identification of CD68+ neutrophil granulocytes in in vitro model of acute inflammation and inflammatory bowel disease

“…However, in contrast to the generally accepted concept of monocyte/macrophage specificity, many authors have reported some reactivity of anti-human CD-68 antibodies with antigens present on the cell surface of various hemato-poietic and non-hematopoietic cells [11][12][13]. Recently published reports demonstrated both at the RNA and protein level that CD-68 was not only expressed in macrophages and monocytes but also expressed by non-myeloid cell types, such as T cells, fibroblasts, endothelial and tumor cells [14,15].…”