Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease

Pallesen, Gorm; Hamilton-Dutoit, Stephen; Rowe, Martin; Young, Lawrence S.

doi:10.1016/0140-6736(91)90943-j

Cited by 651 publications

(264 citation statements)

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“…In contrast, however, abundant expression of CD30 and CD40 has been consistently identified in the great majority of HD cases (26 -29, 31). Furthermore, in a significant portion of cases, HRS cells infected by EBV also commonly express LMP1 proteins (32,33). Interestingly, HRS cells not only express TNFR proteins but also produce several ligands for these receptors as well, including TNF-␣, TNF-␤, LT-␣, and CD30L (26,28,29,37,39,40).…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned previously, TNF-R2, CD30, and CD40 each contain TRAF binding motifs, through which intracellular signaling occurs via interaction with the TRAF proteins. Furthermore, in a significant portion of HD cases, HRS cells express the EBV protein LMP1 (32,33). LMP1 also contains a TRAF-binding domain and uses TRAF proteins in some aspects of its intracellular signaling (8,9,32,33).…”

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Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

et al. 2000

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

et al. 2000

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“…HD is a B-cell lymphoma characterized by the presence of Hodgkin and ReedSternberg (HRS) cells surrounded by a large number of infiltrating nonmalignant cells (Kieff and Rickinson, 2007). Lytic-infected cells are rarely found in EBVpositive HD (Pallesen et al, 1991). BL is an EBVassociated malignancy most commonly located in the abdomen and jaw.…”

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confidence: 99%

Cell transformation mediated by the Epstein–Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling

et al. 2010

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Epstein-Barr virus (EBV) open reading frame BILF1encodes a seven trans-membrane (TM) G protein-coupled receptor that signals with high constitutive activity through Ga i Paulsen et al., 2005). In this paper, the transforming potential of BILF1 is investigated in vitro in a foci formation assay using retrovirally transduced NIH3T3 cells, as well as in vivo by using nude mice. BILF1 revealed a substantial transforming potential that was dependent on constitutive signaling, as a signaling-deficient mutant completely lost its ability to transform cells in vitro, and an intermediately active triple-mutated receptor possessed an intermediate transforming potential. Furthermore, BILF1 expression induced vascular endothelial growth factor secretion in a constitutively active manner. In nude mice, BILF1 promoted tumor formation in 90% of cases, ORF74 (from Kaposi's sarcoma-associated herpes virus) in 100% of cases, whereas the signaling-deficient receptor resulted in tumor establishment in 40% of cases. These data suggest that BILF1, when expressed during EBV infection, could indeed be involved in the pathogenesis of EBV-associated diseases and malignancies. Furthermore, the correlation between receptor activity and the ability to mediate cell transformation in vitro and tumor formation in vivo supports the idea that inverse agonists for BILF1 could inhibit cell transformation and be relevant therapeutic candidates.

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“…1 EBV is transcriptionally active in the tumor cells but expresses only a restricted set of EBV-encoded proteins; expression patterns range from the Epstein-Barr nuclear antigen 1 (EBNA1) only in BL through to EBNA1 plus high levels of both latent membrane proteins 1 and 2 (LMP1, -2) in HD. [2][3][4] EBV-associated carcinomas are intermediate in that EBNA1 and LMP2 appear to be expressed, with or without LMP1. 5 Interestingly many EBV-positive carcinomas also show detectable transcription of a gene, BARF1, which is otherwise thought to be associated only with the virus lytic cycle.…”

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Identification and prevalence of CD8⁺ T‐cell responses directed against Epstein‐Barr virus‐encoded latent membrane protein 1 and latent membrane protein 2

Meij

Leen

Rickinson

et al. 2002

Intl Journal of Cancer

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Epstein-Barr virus (EBV) is associated with several human malignancies that each show different viral gene expressionprofiles. In malignancies such as Hodgkin's disease and nasopharyngeal carcinoma only Epstein-Barr nuclear antigen 1 (EBNA1) and varying levels of latent membrane proteins 1 and 2 (LMP1 and -2) are expressed. Since endogenously expressed EBNA1 is protected from CTL recognition, LMP1 and LMP2 are the most likely target antigens for anti-tumor immunotherapy. Therefore, we sought to identify in a systematic way CD8 ؉ T-cell responses directed against eptitopes derived from LMP1 and LMP2. Using IFN␥-ELISPOT assays of interferon-␥ release, peripheral blood mononuclear cells (PBMC) of healthy donors were screened with peptide panels (15 mer overlapping by 10) spanning the LMP1 and LMP2 sequences of the prototype EBV strain B95.8. When positive responses were found, CD4 ؉ or CD8 ؉ T cells were depleted from donor PBMC to determine the origin of the responder population. We detected CD8 ؉ T-cell responses to LMP1 in 9/50(18%) donors and to LMP2 in 15/28 (54%) donors. In addition to the already described epitopes, 3 new LMP1-and 5 new LMP2-derived CD8 ؉ epitopes were identified. In most donors LMP1-and LMP2-specific CD8 ؉ precursor frequencies were low compared with precursors against immunodominant EBV epitopes from latent (EBNA3A, -3B and -3C) and lytic cycle antigens. These results demonstrate that CD8 ؉ memory T cell responses to LMP1 and especially to LMP2 do exist in Caucasians, albeit at low levels and could potentially be exploited for therapeutic use. © 2002 Wiley-Liss, Inc. Key words: CTL; LMP1; LMP2; Epstein-Barr virusEpstein-Barr virus (EBV) can induce fatal B lymphoproliferative lesions in immunocompromised patients and is etiologically linked to several malignancies arising in the immunocompetent host. Examples of the latter include all cases of endemic Burkitt's lymphoma (BL), all undifferentiated nasopharyngeal carcinomas (NPC), 10% of gastric carcinomas, certain T-/NK-cell lymphomas and 40 -90% of Hodgkin's Disease (HD) cases. 1 EBV is transcriptionally active in the tumor cells but expresses only a restricted set of EBV-encoded proteins; expression patterns range from the Epstein-Barr nuclear antigen 1 (EBNA1) only in BL through to EBNA1 plus high levels of both latent membrane proteins 1 and 2 (LMP1, -2) in HD. 2-4 EBV-associated carcinomas are intermediate in that EBNA1 and LMP2 appear to be expressed, with or without LMP1. 5 Interestingly many EBV-positive carcinomas also show detectable transcription of a gene, BARF1, which is otherwise thought to be associated only with the virus lytic cycle. 6,7 Given the presence of at least some viral antigens in tumor cells, EBV-positive malignancies are potential candidates for immunotherapy. Because endogenously expressed EBNA1 is protected from proteasomal processing and therefore escapes cytotoxic T lymphocyte (CTL) recognition, 8 the prime targets for therapeutic responses in the context of HD and NPC are LMP1 and LMP2. Both are multiple mem...

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Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease

Cited by 651 publications

References 25 publications

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Cell transformation mediated by the Epstein–Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling

Identification and prevalence of CD8⁺ T‐cell responses directed against Epstein‐Barr virus‐encoded latent membrane protein 1 and latent membrane protein 2

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Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease

Cited by 651 publications

References 25 publications

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

Cell transformation mediated by the Epstein–Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling

Identification and prevalence of CD8+ T‐cell responses directed against Epstein‐Barr virus‐encoded latent membrane protein 1 and latent membrane protein 2

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Identification and prevalence of CD8⁺ T‐cell responses directed against Epstein‐Barr virus‐encoded latent membrane protein 1 and latent membrane protein 2