62,710 research outputs found
Relationship Between Non-Hodgkin's Lymphoma and Blood Levels of Epstein-Barr Virus in Children in North-Western Tanzania: A Case Control Study.
No full textNon-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children
Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′
No full textFirst evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)
Epstein-Barr Virus LF2: an Antagonist to Type 1 Interferon
No full textAbstractUpon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway, which is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Despite its association with significant human health problems, activities of Epstein-Barr virus (EBV), a human tumor-inducing herpesvirus, to evade host IFN-mediated innate immunity have not been well characterized. To search for EBV genes that block IFN signal transduction, we carried out a screening of EBV open reading frames for their abilities to block IFN-alpha/beta-mediated luciferase expression upon Sendai virus infection. This screening demonstrates that EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-alpha production and IFN-mediated immunity. This demonstrates a novel immune evasion mechanism of EBV LF2 in blocking cellular IRF7-mediated innate immunity.<br/
James Barr, Sémantique du langage biblique, trad. de l'anglais par D. Auscher et J. Prignaud, 1988
No full textPonthot Joseph. James Barr, Sémantique du langage biblique, trad. de l'anglais par D. Auscher et J. Prignaud, 1988. In: Revue théologique de Louvain, 19ᵉ année, fasc. 4, 1988. p. 495
James Barr, Sémantique du langage biblique, trad. de l'anglais par D. Auscher et J. Prignaud, 1988
No full textPonthot Joseph. James Barr, Sémantique du langage biblique, trad. de l'anglais par D. Auscher et J. Prignaud, 1988. In: Revue théologique de Louvain, 19ᵉ année, fasc. 4, 1988. p. 495
Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition
No full textBackground
Epstein-Barr virus (EBV)-encoded LMP1 protein is commonly expressed in nasopharyngeal carcinoma (NPC). LMP1 is a prime candidate for driving tumourigenesis given its ability to activate multiple signalling pathways and to alter the expression and activity of variety of downstream targets. Resistance to TGFβ-mediated cytostasis is one of the growth transforming effects of LMP1. Of the downstream targets manipulated by LMP1, the induction of Id1 and inactivation of Foxo3a appear particularly relevant to LMP1-mediated effects. Id1, a HLH protein is implicated in cell transformation and plays a role in cell proliferation, whilst Foxo3a, a transcription factor controls cell integrity and homeostasis by regulating apoptosis. The mechanism(s) by which LMP1 induces these effects have not been fully characterised.
Results
In this study, we demonstrate that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1. Furthermore, we show that the induction of Id1 is essential for the transforming function of LMP1 as over-expression of Id1 increases cell proliferation, attenuates TGFβ-SMAD-mediated transcription and renders cells refractory to TGFβ-mediated cytostasis. Id1 silencing in LMP1-expressing epithelial cells abolishes the inhibitory effect of LMP1 on TGFβ-mediated cell growth arrest and reduces the ability of LMP1 to attenuate SMAD transcriptional activity. In response to TGFβ stimulation, LMP1 does not abolish SMAD phosphorylation but inhibits p21 protein expression. In addition, we found the induction of Id1 in LMP1-expressing cells upon stimulation by TGFβ. We provide evidence that LMP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation.
Conclusion
The current data provide novel information regarding the mechanisms by which LMP1 suppresses TGFβ-induced cytostasis, highlighting the importance of Id1 in LMP1 mediated cell transformation
Immunodominance of lytic cycle antigens in Epstein-Barr virus-specific CD4+ T cell preparations for therapy.
No full textEpstein-Barr virus (EBV) is associated with a number of human malignancies. EBV-positive post-transplant lymphoproliferative disease in solid organ and hematopoietic stem cell transplant recipients has been successfully treated by the adoptive transfer of polyclonal EBV-specific T cell lines containing CD4+ and CD8+ T cell components. Although patients receiving T cell preparations with a higher CD4+ T cell proportion show better clinical responses, the specificity of the infused CD4+ component has remained completely unknown.
We generated LCL-stimulated T cell lines from 21 donors according to clinical protocols, and analyzed the antigen specificity of the CD4+ component in EBV-specific T cell preparations using a genetically engineered EBV mutant that is unable to enter the lytic cycle, and recombinantly expressed and purified EBV proteins. Surprisingly, CD4+ T cell lines from acutely and persistently EBV-infected donors consistently responded against EBV lytic cycle antigens and autoantigens, but barely against latent cycle antigens of EBV hitherto considered principal immunotherapeutic targets. Lytic cycle antigens were predominantly derived from structural proteins of the virus presented on MHC II via receptor-mediated uptake of released viral particles, but also included abundant infected cell proteins whose presentation involved intercellular protein transfer. Importantly, presentation of virion antigens was severely impaired by acyclovir treatment of stimulator cells, as currently performed in most clinical protocols.
These results indicate that structural antigens of EBV are the immunodominant targets of CD4+ T cells in LCL-stimulated T cell preparations. These findings add to our understanding of the immune response against this human tumor-virus and have important implications for the improvement of immunotherapeutic strategies against EBV
Epstein-Barr virus latent proteins regulate expression of the anti-apoptotic cellular bfl-1 gene
No full textThe ubiquitous and oncogenic human herpes-virus Epstem-Barr virus (EB V) establishes a latent infection and promotes the long-term survival of the infected host cell by targeting the molecular machinery that controls cell fate decisions, including apoptosis, proliferation and differentiation. These host-virus interactions are likely to play a crucial role in the development of EBV-associated malignancies such, as Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma and tumours in lmmunosuppressed individuals. It has previously been shown in our laboratory that two EBV latent proteins, latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2), which are major effectors of cellular phenotypic change, can independently regulate expression of the cellular bfl-1 gene Bfl-1 is an anti-apoptotic protein of the Bcl-2 family, whose preferential expression in hematopoietic and endothelial cells is controlled by inflammatory stimuli. In this study, it is reported that LMP1 and EBNA2 regulate bfl-1 activity through interactions with components of the NF-kB and Notch signalling pathways respectively NF-kB composed of p65 sub-units trans-activated the bfl-1 promoter m the EBV-negative cell line DG75, and an NF-icB-like binding site at position -52 to -43 relative to the transcription start site was essential for this effect. An RBP-Jk/CBF1 mutant blocked EBNA2-mediated trans-activation of bfl-1 in DG75 cells, indicating an important role for this DNA-binding protein in bfl-1 trans-activation by EBNA2. Although RBP-Jk/CBFI is also essential for signalling by the cellular equivalent of EBNA2, mtra-cellular Notch (NotchIC), this protein was not found to trans-activate the bfl-1 promoter. Both EBNA2 and LMP1 are expressed in EBVmfected cell lines, and EBNA2 is responsible for induction of LMP1 Blocking of either EBNA2- or LMP1-mediated signalling in EBV-mfected cell lines did not dramatically affect the level of bfl-1 promoter activity. However, when both EBNA2 and LMP1 signalling were blocked simultaneously, a significant decrease in the level of bfl-1 activity was observed. These data indicate a role for both EBNA2 and LMP1 in the regulation of the promoter for the bfl-1 gene m the context of the EBV-infected cell. These findings are relevant to our understanding of EBV persistence in the infected host, and its role in malignant disease
Measurement of the B0–B0 oscillation frequency Δmd with the decays B0→D−π+ and B0→ J/ψK∗0
No full textThe B
0
–B
0
oscillation frequency Δmd is measured by the LHCb experiment using a dataset corresponding
to an integrated luminosity of 1.0 fb−1
of proton–proton collisions at √
s = 7 TeV, and is found to be
Δmd
=0.5156±0.0051 (stat.)±0.0033 (syst.) ps−1
. The measurement is based on results from analyses
of the decays B
0
→ D
−π
+ (D
−
→ K
+π
−π
−) and B
0
→ J/ψK
∗0
(J/ψ →μ
+μ
−,K
∗0
→ K
+π
−) and
their charge conjugated modes
Search for the rare decays J/y -> D-s(-) rho(+) and J/psi -> <(D)over bar(0)<(K)over bar*(0)
No full textA search for the rare decays of J/psi -> D-S(-) rho(+) + c.c. and J/psi -> D-S(-)rho(+) + c.c.) <1.3 x 10(-5) and beta(J/psi -
- …
