Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity?

Neipel, Frank; Albrecht, Jens; Fleckenstein, Bernhard

doi:10.1128/jvi.71.6.4187-4192.1997

Cited by 375 publications

(120 citation statements)

References 62 publications

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“…It is a rhadinovirus ( gamma 2 herpesvirus) first detected by representational difference analysis (rda) 5 . HHV‐8 is ∼165 kb long and contains a central region of low‐GC DNA (L DNA) flanked by multi repetitive high GC DNA (H DNA) 26 . Similar to other rhadinoviruses, the L DNA segment of HHV‐8 has many open reading frames with significant homology to cellular genes.…”

Section: Discussionmentioning

confidence: 99%

The clonality of tumor‐infiltrating lymphocytes in African Kaposi’s sarcoma

Nihal¹,

Mikkola²,

Qian³

et al. 2001

J Cutan Pathol

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We conclude that, despite the putative lymphomagenic potential of HHV-8 and EBV and their co-existence in African KS lesions, tumor-infiltrating lymphocytes in these cases do not show evidence of clonal expansion that might be an early manifestation of lymphoma. Nevertheless, these studies are a case in point that sparse lymphoid subpopulations in lesional and uninvolved extranodal tissues can give rise to restricted clonal patterns that must be interpreted carefully to avoid the misdiagnosis of occult lymphoma.

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Section: Discussionmentioning

confidence: 99%

The clonality of tumor‐infiltrating lymphocytes in African Kaposi’s sarcoma

Nihal¹,

Mikkola²,

Qian³

et al. 2001

J Cutan Pathol

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“…implicated in KS, and the presence of HIV-1 further increases the rates of KS by more than 20 000-fold (1)(2)(3)(4)(5). HIV-1 infection appears to contribute directly to KS because other retroviruses (i.e., human T-cell leukemia/lymphoma virus) that also induce immunosuppression do not predispose individuals to develop KS.…”

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confidence: 99%

Human Herpesvirus 8 K1-Associated Nuclear Factor-kappa B-Dependent Promoter Activity: Role in Kaposi's Sarcoma Inflammation?

et al. 2000

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Background:The growing number of human immunodeficiency virus type 1 (HIV-1) infections worldwide and the increasing use of immunosuppressive modalities for organ transplantation have contributed to an epidemic of Kaposi's sarcoma (KS), which has been etiologically linked to human herpesvirus 8 (HHV8) or KS-associated virus. Since the onset of the acquired immunodeficiency syndrome epidemic, inflammation has been recognized as an essential component of KS pathology. HHV8 bears a gene (K1) encoding a transmembrane protein with an immunoreceptor tyrosine-based activation motif. This motif is present in receptors that mediate inflammation. Purpose: To dissect the cellular effects of K1 function and the eventual role of K1 in KS, we developed a cell model for studying K1 expression. Methods: K1 was cloned from BC-3 lymphoma cells. To monitor transcriptional activation, K1 was coexpressed with plasmids containing luciferase under control of various promoters. K1 expression was monitored by indirect immunofluorescence and by combined immunoprecipitation/immunoblot analysis. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Results: Cellular transfection of the K1 gene induced reporter expression under control of nuclear factor-kappa B (NF-B), which controls the transcription of numerous proteins involved in inflammation. Treatment of cells with aspirin, an agent that targets this intracellular pathway and blocks cell inflammatory responses, blocked K1-induced NF-B-dependent promoter activity. When a second KS cofactor, i.e., the HIV-1-transactivating gene tat, was coexpressed with K1, we observed an additive effect on NF-B-dependent transcription. K1 transfection stimulated the secretion of cytokines interleukin (IL) 6, granulocytemacrophage colony-stimulating factor, and IL-12. Cells treated with the conditioned media of K1 transfectants exhibited similar characteristics of K1 transfectants, indicating that a paracrine loop was being activated. Conclusion: Thus,

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“…Sequence analysis methods were used to identify HHV-8 genes with the potential to encode a glycoprotein of 35 to 37 kDa. First, the HHV-8 genomic sequence derived from a KS biopsy specimen (26,27) was searched for open reading frames presumably encoding a polypeptide with a calculated molecular mass ranging from 15 to 40 kDa. A total of 32 open reading frames was selected of which two, K8.1 and K10.1, had not been identified before.…”

Section: Resultsmentioning

confidence: 99%

The Immunogenic Glycoprotein Gp35/37 of Human Herpesvirus 8 Is Encoded by Open Reading Frame K8.1

Neipel¹,

Raab

Albrecht

et al. 1998

Journal of Acquired Immune Deficiency Syndromes and Human Retro

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Human herpesvirus 8 (HHV-8) is likely to be involved in the pathogenesis of Kaposi's sarcoma (KS) and body cavity-based lymphomas (BCBLs). The HHV-8 genome is primarily in a latent state in BCBL-derived cell lines like BCBL-1, but lytic replication can be induced by phorbol esters (R. Renne, W. Zhang, B. Herndier, M. McGrath, N. Abbey, D. Kedes, and D. E. Ganem, Nat. Med. 2:342-346, 1996). A 35-to 37-kDa glycoprotein (gp35-37) is the polypeptide most frequently and intensively recognized by KS patient sera on Western blots with induced BCBL-1 cells. Its apparent molecular mass is reduced to 30 kDa by digestion with peptide-Nglycosidase F. By searching the known HHV-8 genomic sequence for open reading frames (ORF) with the potential to encode such a glycoprotein, an additional, HHV-8-specific reading frame was identified adjacently to ORF K8. This ORF, termed K8.1, was found to be transcribed primarily into a spliced mRNA encoding a glycoprotein of 228 amino acids. Recombinant K8.1 was regularly recognized by KS patient sera in Western blots, and immunoaffinity-purified antibodies to recombinant K8.1 reacted with gp35-37. This shows that the immunogenic gp35-37 is encoded by HHV-8 reading frame K8.1, which will be a useful tool for studies of HHV-8 epidemiology and pathogenesis.

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Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity?

Cited by 375 publications

References 62 publications

The clonality of tumor‐infiltrating lymphocytes in African Kaposi’s sarcoma

The clonality of tumor‐infiltrating lymphocytes in African Kaposi’s sarcoma

Human Herpesvirus 8 K1-Associated Nuclear Factor-kappa B-Dependent Promoter Activity: Role in Kaposi's Sarcoma Inflammation?

The Immunogenic Glycoprotein Gp35/37 of Human Herpesvirus 8 Is Encoded by Open Reading Frame K8.1

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