Induction of bcl-2 expression by epstein-barr virus latent membrane protein 1 protects infected B cells from programmed cell death

Henderson, Scott; Rowe, Martin; Gregory, C. D.; Croom-Carter, Debbie; Wang, Fred; Longnecker, Richard; Kieff, Elliott; Rickinson, Alan B.

doi:10.1016/0092-8674(91)90007-l

Cited by 1,100 publications

(603 citation statements)

References 39 publications

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“…EBNA-1 is constantly expressed by EBV-infected cells in any latency pattern, but the host's immune response never occurs against the molecules (Levitskaya et al, 1995). LMP-1 acts as a direct oncogene to transform epithelial cells morphologically (Fahraeus et al, 1990) and prevent B-lymphoma cells from undergoing apoptosis by up-regulating the expression of cellular bcl-2 (Henderson et al, 1991). We could not detect LMP-1 antigens by immunostaining despite the presence of LMP-1 gene transcripts by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

The latency pattern of Epstein–Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

Iwatsuki

Oyama

et al. 2001

Br J Cancer

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SummaryThe nasal type, extranodal natural killer or T(NK/T)-cell lymphoma is usually associated with latent Epstein-Barr virus (EBV) infection. In order to elucidate the EBV gene expression patterns in vivo, we examined eight patients with cutaneous EBV-related NK/T-cell lymphomas, including six patients with a NK-cell phenotype and two patients with a T-cell phenotype. The implication of EBV in the skin lesions was determined by the presence of EBV-DNA, EBV-encoded nuclear RNA (EBER) and a clonality of EBV-DNA fragments containing the terminal repeats. Transcripts of EBV-encoded genes were screened by reverse transcription-polymerase chain reaction (RT-PCR), and confirmed by Southern blot hybridization. The expression of EBV-related antigens was examined by immunostaining using paraffinembedded tissue sections and cell pellets of EBV-positive cell lines. Our study demonstrated that all samples from the patients contained EBV nuclear antigen (EBNA)-1 mRNA which was transcribed using the Q promoter, whereas both the Q promoter and another upstream promoter (Cp/Wp) were used in EBV-positive cell lines, B95.8, Raji and Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was detected in seven of eight patients and all cell lines, whereas EBNA-2 transcripts were found only in the cell lines. Immunostaining showed no LMP-1, EBNA-2 or ZEBRA antigens in the paraffin-embedded tissue sections, although they were positive in the cell line cells. Latent BHRF1 transcripts encoding bcl-2 homologue and BCRF1 transcripts encoding viral interleukin (vIL)-10 were detected in one and two of eight patients, respectively. A patient with NK-cell lymphoma expressing both transcripts died of rapid progression of the illness. Our results indicate that the restricted expression of the latency-associated EBV genes and the production of vIL-10 and bcl-2 homologue may favour tumour growth, evading the host immune surveillance.

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Section: Discussionmentioning

confidence: 99%

The latency pattern of Epstein–Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

Iwatsuki

Oyama

et al. 2001

Br J Cancer

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“…Here, we have analysed the apoptotic response of human B cells to girradiation focussing on the e ects of expression of the prototype apoptosis-repressor molecule, Bcl-2, and the consequences of activation of the survival pathway triggered by CD40-ligation. Using Burkitt lymphoma cell lines, an established system for modelling human B-cell apoptosis in vitro Henderson et al, 1991;Milner et al, 1992Milner et al, , 1993, we have demonstrated: (1) that radiation-induced apoptosis can be inhibited by Bcl-2, (2) that, whilst Bcl-2 provides a potent short-term survival signal, a proportion of Bcl-2-rescued cells subsequently die in the absence of additional survival signals, (3) that the long-term proliferative capacity of BL cells following irradiation can be either increased or decreased by Bcl-2, depending on the BL line, (4) that these di erences correlate with both di erential e ects of Bcl-2 on cell cycle and di erences in p53 status and (5) that CD40-ligation can inhibit apoptosis in G1-arrested Bcl-2-expressing cells by preventing growth arrest.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of BCL-2 on survival and proliferation of human B-lymphoma cells following γ-irradiation

et al. 1997

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“…Furthermore, LMP1 null EBV mutants can grow in vitro provided the presence of feeder layer, but they fail to generate tumors in SCID mice (Dirmeier et al, 2003). In established B lymphoma lines, LMP1 inhibits apoptosis through upregulation of BCL2 and A20 (Henderson et al, 1991;Laherty et al, 1992). In addition, Kaye et al (1993) have shown that this viral protein is essential for B-cell-transforming capacity of EBV.…”

Section: Ebv Lmp1 Regulates Tcl1 Through Mir-29bmentioning

confidence: 99%

Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b

et al. 2009

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Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is noted for its transforming potential. Yet, it also acts as a cytostatic and growth-relenting factor in Burkitt's lymphoma (BL) cells. The underlying molecular mechanisms of the growth inhibitory property of LMP1 have remained largely unknown. In this study, we show that LMP1 negatively regulates a major oncogene, TCL1, in diffuse large B-cell lymphoma (DLBCL) and BL cells. MicroRNA (miR) profiling of LMP1 transfectants showed that among others, miR-29b, is upregulated. LMP1 diminished TCL1 by inducing miR29b through C-terminus activation region 1 (CTAR1) and CTAR2. miR-29b locked nucleic acid (LNA) antisense oligonucleotide transfection into LMP1-expressing cells reduced miR-29b expression and consequently reconstituted TCL1, suggesting that LMP1 negatively regulates TCL1 through miR-29b upregulation. The miR-29b increase by LMP1 was due to an increase in the cluster pri-miR-29b1-a transcription, derived from human chromosome 7. Using pharmacological inhibitors, we found that p38 mitogen-activated protein kinase-activating function of LMP1 is important for this effect. The ability of LMP1 to negatively regulate TCL1 through miR-29b might underlie its B-cell lymphoma growth antagonistic property. As LMP1 is also important for B-cell transformation, we suggest that the functional dichotomy of this viral protein may depend on a combination of levels of its expression, lineage and differentiation of the target cells and regulation of miRs, which then directs the outcome of the cellular response.

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Induction of bcl-2 expression by epstein-barr virus latent membrane protein 1 protects infected B cells from programmed cell death

Cited by 1,100 publications

References 39 publications

The latency pattern of Epstein–Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

The latency pattern of Epstein–Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

Differential effects of BCL-2 on survival and proliferation of human B-lymphoma cells following γ-irradiation

Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b

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