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Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma (KS) herpesvirus, can cause KS but is inefficient. Untreated human immunodeficiency virus type 1 (HIV-1) coinfection is a powerful risk factor. The HHV-8 chemokine receptor, vGPCR (ORF74), activates NF-κB and NF-AT, and their levels of activation, are synergistically increased by HIV-1 Tat. Transgenic vGPCR mice develop KS-like tumors. A cell line derived from one such tumor expresses vGPCR and forms tumors in nude mice. Here we show that transfection of DNA encoding HIV-1 tat (but not a transactivation-defective mutant) into these tumor cells increases NF-κB and NF-AT activation levels and accelerates tumor formation. Tumorigenesis was also accelerated when Tat DNA was transfected into normal cells and the transfected cells were mixed with the tumor cells and injected into a single site. Tumorigenesis was also increased when the two cell types were injected at separate sites, suggesting that tumorigenesis is accelerated by Tat through soluble factors. [ABSTRACT FROM AUTHOR]

The product of human herpesvirus 8 (HHV-8) open reading frame 74 (ORF74) is related structurally and functionally to cellular chemokine receptors. ORF74 activates several cellular signaling pathways in the absence of added ligands, and NIH 3T3 cells expressing ORF74 are tumorigenic in nude mice. We have generated a line of transgenic (Tg) mice with ORF74 driven by the simian virus 40 early promoter. A minority (approximately 30%) of the Tg mice, including the founder, developed tumors resembling Kaposi's sarcoma (KS) lesions, which occurred most typically on the tail or legs. The tumors were highly vascularized, had a spindle cell component, expressed VEGF-C mRNA, and contained a majority of CD31[sup +] cells. CD31 and VEGF-C are typically expressed in KS. Tumors generally (but not always) occurred at single sites and most were relatively indolent, although several mice developed large visceral tumors. ORF74 was expressed in a minority of cells in the Tg tumors and in a few other tissues of mice with tumors; mice without tumors did not express detectable ORF74 in any tissues tested. Cell lines established from tumors expressed ORF74 in a majority of cells, expressed VEGF-C mRNA, and were tumorigenic in nude mice. The resultant tumors grew rapidly, metastasized, and continued to express ORF74. Cell lines established from these secondary tumors also expressed ORF74 and were tumorigenic. These data strongly suggest that ORF74 plays a role in the pathology of KS and confirm and extend previous findings on the tumorigenic potential of ORF74. [ABSTRACT FROM AUTHOR]

Identifies a novel viral Bcl-2 homolog, designated KSbcl-2, from human herpesvirus 8 (HHV8) or Kaposi sarcoma-associated herpesvirus. Encoding of a bcl-2 homolog by HHV8; Inhibition of Sindbis virus-induced apoptosis by the overexpression of KSbcl-2; Expression of KSbcl-2 during the lytic viral replication cycle.

Presents information on a study which focused on the genome characteristics of gamma herpesviruses (KSHV) and its gentic aspects. Information on the availibility of five distinct gamma herpesviruses to assist in the completion of genomic deoxyribonucleic acid (DNA) sequences; Features of the KSHV; Methodology used to conduct the study; Discussion on the results from the study.

Background: Human herpesvirus 8 (HHV-8) DNA sequences have been detected in Kaposi's sarcoma, in primary effusion lymphoma (an unusual high-grade non-Hodgkin's lymphoma seen primarily in patients with acquired immunodeficiency syndrome [AIDS]), and in Castleman's disease (a rare lymphoproliferative disorder); however, proof that HHV-8 is involved in the pathogenesis of these diseases remains to be established. HHV-8 contains a gene, i.e., v-cyclin D, that is a homologue of the cellular cyclin D2 gene, which encodes a protein that promotes passage through G1 phase of the cell cycle. Previous studies have identified v-cyclin D messenger RNA (mRNA) in biopsy specimens of Kaposi's sarcoma. In this study, we isolated a full-length v-cyclin D complementary DNA and characterized the pattern of v-cyclin D mRNA expression in Kaposi's sarcoma.Methods: Standard methods were used to construct and to screen HHV-8 genomic and complementary DNA libraries. Reverse transcription-polymerase chain reaction (RT-PCR) methods and in situ hybridization with RNA probes were used to examine v-cyclin D mRNA expression.Results: RT-PCR demonstrated the presence of v-cyclin D mRNA in biopsy specimens of AIDS-related Kaposi's sarcoma, in early-passage spindle cells from classical (i.e., not AIDS-related) Kaposi's sarcoma, and in spindle cells isolated from the peripheral blood of patients with AIDS-related Kaposi's sarcoma. In situ hybridization indicated that mRNAs for v-cyclin D and kaposin, an HHV-8 latency-associated gene, were present in approximately 1% of the spindle cells in early patch lesions and approximately 60% of the spindle cells in late nodular lesions of Kaposi's sarcoma.Conclusions: Spindle cells of Kaposi's sarcoma, which have been regarded as the tumor cells of this cancer, contain v-cyclin D mRNA. Expression of v-cyclin D protein may be involved in the pathogenesis of Kaposi's sarcoma by promoting cell proliferation. [ABSTRACT FROM AUTHOR]