Kaposi's sarcoma: further immunohistologic evidence of a vascular endothelial origin

Kraffert, C.

doi:10.1001/archderm.127.11.1734

Cited by 17 publications

(10 citation statements)

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“…Whether spindle cells are derived from vascular or lymphatic precursors has been controversial (143,240,270,318,529,539). A new monoclonal antibody that recognizes an O-linked sialoglycoprotein reinforces the argument for a lymphatic origin of these cells.…”

Section: Histopathogenesis Of Ks and Its Relationship To Kshv Infectionmentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection

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Section: Histopathogenesis Of Ks and Its Relationship To Kshv Infectionmentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

View full text Add to dashboard Cite

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“…Instead, it appears to be a hyperplastic disorder caused, in part, by local production of inflammatory cytokines such as interleukin 1 (IL-1), IL-6, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣) and growth factors such as basic fibroblast growth factor and vascular endothelial growth factor (11)(12)(13)(14). This is supported by the fact that infiltration of inflammatory cells in KS lesions, including CD8 ϩ T cells, monocytes, macrophages, and dendritic cells, precedes transformation of the spindle-shaped endothelial cells (3,26,39). Infiltrating cells systematically produce inflammatory cytokines that are likely responsible for activation of vessels and endothelial cells, increase of adhesiveness with extravasation, and recruitment of lymphocytes and monocytes (10,12).…”

mentioning

confidence: 94%

Kaposi's Sarcoma-Associated Herpesvirus OX2 Glycoprotein Activates Myeloid-Lineage Cells To Induce Inflammatory Cytokine Production

Chung

Means

Choi

et al. 2002

J Virol

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Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative disease which is triggered by infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV contains an open reading frame, K14, that has significant homology with cellular OX2, designated viral OX2 (vOX2). In this report, we demonstrate that vOX2 encodes a glycosylated cell surface protein with an apparent molecular mass of 55 kDa. Purified glycosylated vOX2 protein dramatically stimulated primary monocytes, macrophages, and dendritic cells to produce the inflammatory cytokines interleukin 1␤ (IL-1␤), IL-6, monocyte chemoattractant protein 1, and TNF-␣. Furthermore, expression of vOX2 on B lymphocytes stimulated monocytes to produce inflammatory cytokines in mixed culture. These results demonstrate that like its cellular counterpart, vOX2 targets myeloidlineage cells, but unlike cellular OX2, which delivers a restrictive signal, KSHV vOX2 provides an activating signal, resulting in the production of inflammatory cytokines. Thus, this is a novel viral strategy where KSHV has acquired the cellular OX2 gene to induce inflammatory cytokine production, which potentially promotes the cytokine-mediated angiogenic proliferation of KSHV-infected cells.

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“…Instead, it appears to be a hyperplastic disorder caused, in part, by local production of inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣), as well as growth factors, such as basic fibroblast growth factor and vascular endothelial growth factor (11)(12)(13)(14). This is supported by the fact that infiltration of inflammatory cells, including CD8 ϩ T cells, monocytes, macrophages, and dendritic cells, precedes transformation of the spindle-shaped endothelial cells (3,21,35). Infiltrating cells systematically produce inflammatory cytokines that are likely responsible for activating vessels and endothelial cells, increasing adhesiveness with extravasation, and recruiting lymphocytes and monocytes (10,12).…”

mentioning

confidence: 95%

Structural Analysis of the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein

Lee¹,

Connole

Tang

et al. 2003

J Virol

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The K1 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently transduces extracellular signals to elicit cellular activation events through its cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). In addition, the extracellular domain of K1 demonstrates regional homology with the immunoglobulin (Ig) family and contains conserved regions (C1 and C2) and variable regions (V1 and V2). To generate mouse monoclonal antibodies directed against the KSHV K1 protein, BALB/c mice were primed and given boosters with K1 protein purified from mammalian cells. Twenty-eight hybridomas were tested for reactivity with K1 protein by enzyme-linked immunosorbent assay, immunofluorescence, flow cytometry, immunohistochemistry, and immunoblotting. Deletion mutants of the K1 extracellular domain were used to map the epitope of each antibody. All antibodies were directed to the Ig, C1, and C2 regions of K1. Furthermore, antibody recognition of a short sequence (amino acids 92 to 125) of the C2 region overlapping with the Ig region of K1 efficiently induced intracellular free calcium mobilization; antibody recognition of the other regions of K1 did not. The efficient signal transduction of K1 induced by antibody stimulation required both the ITAM sequence of the cytoplasmic domain and the normal structure of the extracellular domain. Finally, immunological assays showed that K1 was expressed during the early lytic cycle of viral replication in primary effusion lymphoma cells. K1 was readily detected in multicentric Castleman's disease tissues, whereas it was not detected in Kaposi's sarcoma lesions, suggesting that K1 is preferentially expressed in lymphoid cells. Thus, these results indicate that the conserved regions, particularly the Ig and C2 regions, of the K1 extracellular domain are exposed on the outer surface and play an important role in K1 structure and signal transduction, whereas the variable regions of K1 appear to be away from the surface.

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Kaposi's sarcoma: further immunohistologic evidence of a vascular endothelial origin

Cited by 17 publications

References 0 publications

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Kaposi's Sarcoma-Associated Herpesvirus OX2 Glycoprotein Activates Myeloid-Lineage Cells To Induce Inflammatory Cytokine Production

Structural Analysis of the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein

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