FROM BURKITT'S LYMPHOMA TO CHRONIC ACTIVE EPSTEIN-BARR VIRUS (EBV) INFECTION: An Expanding Spectrum of EBV-Associated Diseases

Okano, Motohiko; Gross, Thomas G.

doi:10.1080/088800101750476014

Cited by 15 publications

(6 citation statements)

References 63 publications

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“…In this study, we further extended our previous observation to investigate the EBV gene product(s) responsible for upregulation of the TNF· gene. EBV gene expression in EBV-infected T cell lymphoma lines was demonstrated to belong to a type II latency with expression of EBNA-1, LMP-1, and LMP-2a, while a type III latency with expression of EBNA-1, EBNA-2, LMP-1, and lytic BZLF transcripts was detected in EBV-infected B cell lines, results consistent with previous reports in lymphoma tissues [5,9,28,36,38]. By CAT and luciferase-reporter assays of various expression constructs of EBV genes, we demonstrated that LMP-1 is the candidate gene product responsible for the upregulation of TNF·.…”

Section: Discussionsupporting

confidence: 81%

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-α in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

Lay¹,

Chuang²,

Rowe³

et al. 2003

J Biomed Sci

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The infection of human T cells by Epstein-Barr virus (EBV) may result in a fatal hemophagocytic syndrome (HS). We have previously shown that EBV can selectively upregulate the tumor necrosis factor-α (TNFα) gene and lead to activation of macrophages in a manner similar to the pathobiology of HS in EBV-infected T lymphoproliferative disorders (LPDs). This study was designed to further clarify the specific EBV gene product(s) responsible for TNFα upregulation. RT-PCR analysis of EBV gene expression was performed on 2 CR2-transfected EBV-infected T lymphoma lines and 2 EBV-infected B cell lines. To identify the EBV gene responsible for upregulation of TNFα, 2 reporter recombinant plasmids, pTNFα-CAT and pTNFα-Luc, were then constructed and cotransfected with the expression plasmids of the EBV latent and lytic genes (EBNA-1, EBNA-2, LMP-1, LMP-2A, and BZLF-1) in both T and B cell lines. Analyses using ELISA and Western blotting were further performed to detect the secreted TNFα. The results revealed that EBNA-1 and LMP-1 were consistently expressed in EBV-infected T cell lines (type II latency), while a type III latency with expression of EBNA-1, EBNA-2, LMP-1, and lytic BZLF transcripts was detected in EBV-infected B cell lines. LMP-1 was demonstrated to be the only EBV gene product to transactivate the TNFα gene, and this phenomenon was observed only in T, not in B, cells. Enhanced secretion of TNF-α protein was also detected in LMP1-transfected T cell lines. We concluded that LMP1 is the candidate protein in the upregulation of the TNFα gene in T cells and is probably responsible for the pathogenesis of HS in EBV-infected T lymphoproliferative disorders.

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Section: Discussionsupporting

confidence: 81%

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-α in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

Lay¹,

Chuang²,

Rowe³

et al. 2003

J Biomed Sci

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“…The endemic form is found mainly in Africa and is characterized by infection with Epstein-Barr virus (EBV) [74,75]. In contrast, an association with EBV infection is found in only about 20% of sporadic BL, but chronic infection with another, as yet unidentified microbe might well figure in the remainder.…”

Section: Discussionmentioning

confidence: 99%

The B Cell Antigen Receptor and Overexpression of MYC Can Cooperate in the Genesis of B Cell Lymphomas

et al. 2008

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A variety of circumstantial evidence from humans has implicated the B cell antigen receptor (BCR) in the genesis of B cell lymphomas. We generated mouse models designed to test this possibility directly, and we found that both the constitutive and antigen-stimulated state of a clonal BCR affected the rate and outcome of lymphomagenesis initiated by the proto-oncogene MYC. The tumors that arose in the presence of constitutive BCR differed from those initiated by MYC alone and resembled chronic B cell lymphocytic leukemia/lymphoma (B-CLL), whereas those that arose in response to antigen stimulation resembled large B-cell lymphomas, particularly Burkitt lymphoma (BL). We linked the genesis of the BL-like tumors to antigen stimulus in three ways. First, in reconstruction experiments, stimulation of B cells by an autoantigen in the presence of overexpressed MYC gave rise to BL-like tumors that were, in turn, dependent on both MYC and the antigen for survival and proliferation. Second, genetic disruption of the pathway that mediates signaling from the BCR promptly killed cells of the BL-like tumors as well as the tumors resembling B-CLL. And third, growth of the murine BL could be inhibited by any of three distinctive immunosuppressants, in accord with the dependence of the tumors on antigen-induced signaling. Together, our results provide direct evidence that antigenic stimulation can participate in lymphomagenesis, point to a potential role for the constitutive BCR as well, and sustain the view that the constitutive BCR gives rise to signals different from those elicited by antigen. The mouse models described here should be useful in exploring further the pathogenesis of lymphomas, and in preclinical testing of new therapeutics.

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“…EBV is one of DNA viruses belonging to the herpes virus family, which consists of 172 kilobase double-stranded DNA [4]. Since EBV was discovered in tumor cells of Burkitt's lymphoma in 1964, the spectrum of EBV-associated human disease has been expanded and includes infectious mononucleosis, nasopharyngeal carcinoma, gastric lymphoepithelioma-like carcinoma, gastric adenocarcinoma, leiomyosarcoma, leiomyoma, and lymphoproliferative disorder of various type [10].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Epstein-Barr virus associated childhood non-Hodgkin’s lymphoma in the Republic of Korea

Kim

Suh

et al. 2005

Virchows Arch

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To analyze the clinicopathologic characteristics of childhood non-Hodgkin's lymphoma (NHL) associated with Epstein-Barr virus (EBV), EBER in situ hybridization was performed in 80 cases of NHLs. EBER-positive lymphomas account for 25% (20/80) and include NK/T-cell lymphoma (6/6), aggressive NK-cell leukemia (1/1), peripheral T cell lymphoma (5/11), diffuse large B-cell lymphoma (5/14), hydroa-like T-cell lymphoma (1/1), marginal zone B-cell lymphoma (1/2), and post-transplantation lymphoproliferative disorder (1/1). Other types including 19 cases of Burkitt's lymphoma were negative. For 9 EBER-positive cases, immunohistochemical staining for LMP-1, and EBNA-2 was performed to determine the EBV latency pattern. Two of nine EBER-positive cases expressed both LMP-1 and EBNA-2. Clinically, patients with EBV-positive B-cell lymphomas were cured with chemotherapy, whereas EBV-associated NK- and T cell lymphomas pursued fatal clinical course. In conclusion, EBVs infected in childhood NHLs are frequently associated not only with NK- and T- cell lymphomas but also large B-cell lymphomas.

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FROM BURKITT'S LYMPHOMA TO CHRONIC ACTIVE EPSTEIN-BARR VIRUS (EBV) INFECTION: An Expanding Spectrum of EBV-Associated Diseases

Cited by 15 publications

References 63 publications

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-α in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-α in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

The B Cell Antigen Receptor and Overexpression of MYC Can Cooperate in the Genesis of B Cell Lymphomas

Characteristics of Epstein-Barr virus associated childhood non-Hodgkin’s lymphoma in the Republic of Korea

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FROM BURKITT'S LYMPHOMA TO CHRONIC ACTIVE EPSTEIN-BARR VIRUS (EBV) INFECTION: An Expanding Spectrum of EBV-Associated Diseases

Cited by 15 publications

References 63 publications

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-&alpha; in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-&alpha; in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

The B Cell Antigen Receptor and Overexpression of MYC Can Cooperate in the Genesis of B Cell Lymphomas

Characteristics of Epstein-Barr virus associated childhood non-Hodgkin’s lymphoma in the Republic of Korea

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Product

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Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-α in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome

Epstein-Barr Virus Latent Membrane Protein-1 Mediates Upregulation of Tumor Necrosis Factor-α in EBV-Infected T Cells: Implications for the Pathogenesis of Hemophagocytic Syndrome