4,306 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
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
Cervical cancer with Human Papilloma Virus and Epstein Barr Virus positive
No full textThe Early-7 (E7) protein of HPV binds to the underphosphorelated form of the tumor suppressor
protein – pRb and displaces the E2F transcription factor that is normally bound by pRb. The latent
membrane protein-1 (LMP-1) of EBV prevents apoptosis of B cells by up regulating the expression
of bcl-2, and it activates growth promoting pathway that are normally triggered by T cell – derivate
signal. The aims of this study to know that in cervical cancer stay HPV and EBV.
DNA was isolated from nineteen sample cervical cancer tissues frozen section. Diagnose related
with HPV and EBV was made by Polymerase Chains Reaction (PCR).
The result of this experiment showed that from 19 samples diagnosed as cervical cancer, 17
samples are positive HPV and 13 samples had HPV and EBV positive. The conclusion of this
experiment is 89% of cervical cancers are infected with HPV and 68% also infected with HPV and
EBV
Complexities associated with expression of Epstein-Barr virus (EBV) lytic origins of DNA replication.
No full textEBV has two lytic origins (oriLyt) of DNA replication lying at divergent sites on the viral genome within a duplicated sequence (DS). The latter contains potential hairpin loops, ‘hinge’ elements and the promoters for transcripts from viral genes BHLF1 and LF3. These genes themselves consist largely of 125 and 102 bp repetitive sequences, respectively, and encode basic proteins. We have examined these genomic regions in detail in attempts to understand why lytic replication—necessary for virus survival—is so inefficient, and to identify controlling elements. Our studies uncovered a diverse family of promoters (P) for BHLF1 and LF3, only one pair of which (P1) proved sensitive to chemical inducing agents. The others (P2–P3/4), abutting the replication ‘core’ origin elements in DS and extending into 50-unique sequences, may play roles in the maintenance of viral latency. We further identified a family of overlapping small complementary-strand RNAs that transverse the replication ‘core’ origin elements in a manner suggesting a role for them as ‘antisense’ species and/or DNA replication primers. Our data are discussed in terms of alternative lytic replication models. We suggest our findings might prove useful in seeking better control over viral lytic replication and devising strategies for therapy
Micro RNAs of Epstein-Barr virus promote cell cycle progression and prevent apoptosis of primary human B cells.
No full textCellular and viral microRNAs (miRNAs) are involved in many different processes of key importance and more than 10,000 miRNAs have been identified so far. In general, relatively little is known about their biological functions in mammalian cells because their phenotypic effects are often mild and many of their targets still await identification. The recent discovery that Epstein-Barr virus (EBV) and other herpesviruses produce their own, barely conserved sets of miRNAs suggests that these viruses usurp the host RNA silencing machinery to their advantage in contrast to the antiviral roles of RNA silencing in plants and insects. We have systematically introduced mutations in EBV's precursor miRNA transcripts to prevent their subsequent processing into mature viral miRNAs. Phenotypic analyses of these mutant derivatives of EBV revealed that the viral miRNAs of the BHRF1 locus inhibit apoptosis and favor cell cycle progression and proliferation during the early phase of infected human primary B cells. Our findings also indicate that EBV's miRNAs are not needed to control the exit from latency. The phenotypes of viral miRNAs uncovered by this genetic analysis indicate that they contribute to EBV-associated cellular transformation rather than regulate viral genes of EBV's lytic phase
Messenger RNA Sequence Rather than Protein Sequence Determines the Level of Self-synthesis and Antigen Presentation of the EBV-encoded Antigen, EBNA1
No full textpeer-reviewedViruses establishing persistent latent infections have evolved various mechanisms to avoid immune surveillance. The Epstein-Barr virus-encoded nuclear antigen, EBNA1, expressed in all EBV-associated malignancies, modulates its own protein levels at quantities sufficient to maintain viral infection but low enough so as to minimize an immune response by the infected host cell. This evasion mechanism is regulated through an internal purine-rich mRNA repeat sequence encoding glycine and alanine residues. In this study we assess the impact of the repeat's nucleotide versus peptide sequence on inhibiting EBNA1 self-synthesis and antigen presentation. We demonstrate that altered peptide sequences resulting from frameshift mutations within the repeat do not alleviate the immune-evasive function of EBNA1, suggesting that the repetitive purine-rich mRNA sequence itself is responsible for inhibiting EBNA1 synthesis and subsequent poor immunogenicity. Our comparative analysis of the mRNA sequences of the corresponding repeat regions of different gammaherpesvirus maintenance homologues to EBNA1 highlights the high degree of identity between the nucleotide sequences despite very little homology in the encoded amino acid sequences. These studies demonstrate the importance of gammaherpesvirus purine-rich mRNA repeat sequences on antigenic epitope generation and evasion from T-cell mediated immune control, suggesting novel approaches to prevention and treatment of latent infection by this class of virus.National Health & Medical Research Council (NH&MRC) Canberra, Australia (#496684 APP1005091); NH&MRC Career Development Award Research Fellowship (#496712
Conditional immortalization of human B cells by CD40 ligation
No full textIt is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It was shown earlier that human B cells from peripheral blood of healthy donors can be efficiently induced to proliferate for up to ten weeks in vitro by stimulating their receptor CD40 in the presence of interleukin-4. When we applied the same stimuli under conditions of modified cell number and culture size, we were surprised to find that our treatment induced B cells to proliferate throughout an observation period of presently up to 1650 days, representing more than 370 population doublings, which suggested that these B cells were immortalized in vitro. Long-term CD40-stimulated B cell cultures could be established from most healthy adult human donors. These B cells had a constant phenotype, were free from Epstein-Barr virus, and remained dependent on CD40 ligation. They had constitutive telomerase activity and stabilized telomere length. Moreover, they were susceptible to activation by Toll-like receptor 9 ligands, and could be used to expand antigen-specific cytotoxic T cells in vitro. Our results indicate that human somatic cells can evade senescence and be conditionally immortalized by external stimulation only, without a requirement for genetic manipulation or oncoviral infection. Conditionally immortalized human B cells are a new tool for immunotherapy and studies of B cell oncogenesis, activation, and function
Identification and Functional Analysis of Epstein-Barr Nuclear Antigen 2 (EBNA2) Target Genes
No full textUtilising proteomic approaches to understand oncogenic human herpesviruses
No full textThe γ‑herpesviruses Epstein-Barr virus and Kaposi's sarcoma‑associated herpesvirus are successful pathogens, each infecting a large proportion of the human population. These viruses persist for the life of the host and may each contribute to a number of malignancies, for which there are currently no cures. Large‑scale proteomic-based approaches provide an excellent means of increasing the collective understanding of the proteomes of these complex viruses and elucidating their numerous interactions within the infected host cell. These large‑scale studies are important for the identification of the intricacies of viral infection and the development of novel therapeutics against these two important pathogens
Acute Epstein-Barr virus infection causing bilateral conjunctival hemorrhages
No full textThe systemic and ocular manifestations of acute Epstein-Barr virus infection are protean. Conjunctival hemorrhage has been described once. This report describes a young male who had bilateral conjunctival hemorrhages in the setting of acute Epstein-Barr virus infection. Copyright © 2005 by The Southern Medical Association.Aburn NS, 1996, OPHTHALMOLOGY, V103, P776; Feinberg AS, 2000, OPHTHALMOLOGY, V107, P159, DOI 10.1016-S0161-6420(99)00014-7; GARDNER BP, 1991, AM J OPHTHALMOL, V112, P567; Heiligenhaus A, 2001, EYE, V15, P792; MATOBA AY, 1986, OPHTHALMOLOGY, V93, P746; MATOBA AY, 1990, SURV OPHTHALMOL, V35, P145, DOI 10.1016-0039-6257(90)90069-8; MEISLER DM, 1981, AM J OPHTHALMOL, V92, P722; PFLUGFELDER SC, 1993, INT OPHTHALMOL CLIN, V33, P95, DOI 10.1097-00004397-199303310-00009; STRAUS SE, 1993, ANN INTERN MED, V118, P45; USUI M, 1990, INT OPHTHALMOL, V14, P371, DOI 10.1007-BF00163559; WILHELMUS KR, 1981, AM J OPHTHALMOL, V89, P11720
- …
