Detection of Epstein-Barr virus in posttransplantation T cell lymphoma in a kidney transplant recipient: case report and review.
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Posttransplantation T cell lymphomas (PTTLs) are rather unusual, and their etiology remains unclear. We describe a case of Epstein-Barr virus (EBV)-associated small bowel T cell lymphoma in a patient 5 years after kidney transplantation. EBV was detected in a biopsy sample by in situ hybridization, immunohistochemical staining, and polymerase chain reaction analysis. Eight previously reported cases of EBV-associated PTTL are reviewed, in which special attention is paid to the methods used for assessing EBV. This case of EBV-associated PTTL is believed to be the most completely studied from the point of view of the methods used for detection of EBV. The prognosis of PTTL is poor, but it has been reported that therapeutic approaches can be successful if they are given early in the course of the illness. Therefore, it is necessary to improve the diagnosis PTTL and to assess the precise involvement of EBV in posttransplantation lymphoproliferative disorders. (+info)
Coinfection of multiple strains of Epstein-Barr virus in immunocompetent normal individuals: reassessment of the viral carrier state.
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This study reassesses the occurrence of Epstein-Barr virus (EBV) diversity and coinfection versus dominance of a single viral strain within immunocompetent normal carriers. Polymerase chain reaction analysis of several different polymorphic loci of the EBV genome was performed on collections of peripheral blood mononuclear cells and multiple lymphoid and epithelial tissues of the same individuals. Autopsy specimens from 15 individuals who died of causes unrelated to EBV infection served as normal viral carriers. Unexpectedly, coinfection of multiple distinct strains of EBV of the same type (usually type 1) and less frequently of both types 1 and 2 was found to be very high within individual viral carriers. These data indicate that coinfection with multiple EBV strains is much more prevalent in normal carriers than previously appreciated, which in turn has direct implications on EBV persistence, host-viral interaction and pathogenesis. (+info)
Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents.
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A UK population-based case-control study of Hodgkin's disease (HD) in young adults (16-24 years) included 118 cases and 237 controls matched on year of birth, gender and county of residence. The majority (103) of the cases were classified by Epstein-Barr virus (EBV) status (EBV present in Reed-Stenberg cells), with 19 being EBV-positive. Analyses using conditional logistic regression are presented of subject reports of prior infectious disease (infectious mononucleosis (IM), chicken pox, measles, mumps, pertussis and rubella). In these analyses HD cases are compared with matched controls, EBV-positive cases and EBV-negative cases are compared separately with their controls and formal tests of differences of association by EBV status are applied. A prior history of IM was positively associated with HD (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.10-5.33) and with EBV-positive HD (OR = 9.16, 95% CI = 1.07-78.31) and the difference between EBV-positive and EBV-negative HD was statistically significant (P = 0.013). The remaining infectious illnesses (combined) were negatively associated with HD, EBV-positive HD and EBV-negative HD (in the total series, for > or =2 episodes compared with < or =1, OR = 0.45, 95% CI = 0.25-0.83). These results support previous evidence that early exposure to infection protects against HD and that IM increases subsequent risk; the comparisons of EBV-positive and EBV-negative HD are new and generate hypotheses for further study. (+info)
The Epstein-Barr virus and its association with human cancers.
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The Epstein-Barr virus (EBV) has been linked to the development of a variety of human malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, some T cell lymphomas, post-transplant lymphoproliferative disease, and more recently, certain cancers of the stomach and smooth muscle. This review summarizes these associations and in particular the role of the viral latent genes in the transformation process. (+info)
Differential cytokine expression in EBV positive peripheral T cell lymphomas.
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AIM: To investigate whether specific cytokines are secreted locally at the tumour site in Epstein-Barr virus (EBV) positive peripheral T cell lymphoma (PTCL). METHODS: An RNase protection assay system was used to study the differential expression of 21 cytokines in parallel in eight cases of EBV positive non-nasal PTCL, and compared with 11 EBV negative non-nasal PTCLs and three EBV positive nasal natural killer (NK) cell lymphomas. RESULTS: Among the eight EBV positive cases, interferon gamma (IFN-gamma), lymphotoxin beta (LT beta), interleukin 10 (IL-10), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and IL-1 receptor a (IL-Ra) were frequently detectable. IL-15, IL-6, IL-4, IL-1 beta, TNF-beta, and IL-9 were sporadically detectable. Of the frequently detectable cytokines, IFN-gamma and LT beta were commonly detected in the EBV negative cases. For cases with > 50% EBV encoded small non-polyadenylated RNA (EBER) positive cells, IL-10, TNF-alpha, and TGF-beta 1 were detected in three of three cases, and IL-1Ra in two of three cases. For cases with < 20% EBER positive cells, IL-10 was detected in three of five cases, TNF-alpha in two of four cases, but TGF-beta 1 and IL-1Ra were not detected. Interestingly, IL-6 was detected in two of three cases with > 50% EBER positive cells, but only in one of five cases with < 20% EBER positive cells. For comparison, in NK cell lymphomas, IL-10, TNF-alpha, IL-1Ra, and IL-6 were all detectable, but TGF-beta 1 was not detected at all. Immunohistochemical staining revealed IL-10 in many cells; in contrast, EBV latent membrane protein 1 (LMP1) was only found to be positive in isolated cells. CONCLUSIONS: Certain cytokines, such as IL-10 and TNF-alpha, might be expressed preferentially in EBV positive peripheral T cell lymphomas. It is likely that such a cytokine environment enhances EBV infection and contributes towards tumorigenesis. (+info)
Epidemiology of herpesvirus papio infection in a large captive baboon colony: similarities to Epstein-Barr virus infection in humans.
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The epidemiology of herpesvirus papio, a lymphocryptovirus similar to Epstein-Barr virus (EBV), was studied in a captive colony of >1900 baboons. Herpesvirus papio IgG antibody titers were measured by IFA. In total, 438 specimens from 296 baboons were assessed, including 116 serial specimens from 52 juveniles and 6 infants studied monthly for 1 year following birth and at age 18 months. Maternally derived antibody reached a nadir at 4 months of age. About 75% of animals at 12 months of age and >95% of animals after age 24 months demonstrated serologic evidence of herpesvirus papio infection. After age 3 years, the geometric mean titer was 1:60-75. The epidemiology of herpesvirus papio infection in baboons closely parallels that of EBV infection in humans. An animal model of lymphocryptovirus infection will facilitate investigations of human lymphocryptovirus biology. (+info)
Detection of lymphocytes productively infected with Epstein-Barr virus in non-neoplastic tonsils.
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Epstein-Barr virus (EBV) persists for life in the infected host. Little is known about EBV reactivation and regulation of virus persistence in healthy individuals. We examined tonsils of chronic tonsillitis patients to detect EBV transcripts, EBV genomes and lytic proteins. LMP1 transcripts were observed in 11 of 15 specimens and BZLF1 transcripts were detected in six. Multiple copies of EBV genome equivalents per cell, and ZEBRA- and viral capsid antigen-positive cells were also detected in tonsillar lymphocytes. These results indicate that EBV productively infected cells may survive in the face of immune surveillance in the tonsils. Thus, EBV replication may occur in tonsillar lymphocytes, and tonsillar lymphoid tissues may play a role in the maintenance of EBV load in vivo. (+info)
A novel approach for nasopharyngeal carcinoma treatment uses phenylbutyrate as a protein kinase C modulator: implications for radiosensitization and EBV-targeted therapy.
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Sodium phenylbutyrate (NaPB) represent a new non-toxic class of compounds with antiproliferative activities to different tumors and has been shown to modulate many gene expressions by inhibiting histone deacetylation and DNA methylation as the major mechanism. Butyrate and other protein kinase C (PKC) activators have been reported to be able to activate virus enzymes. The present work investigates whether NaPB has an antiproliferative effect or modulatory effects on EBV-associated nasopharyngeal carcinoma (NPC) and whether EBV thymidine kinase gene can be activated to make cells susceptible to ganciclovir (GCV) therapy. NaPB treatment displayed a dose- and time-dependent antiproliferative effect on the NPC cell line CNE2. Cell cycle analysis revealed an inhibitory effect of NaPB on G1-S-phase progression. Shortly after NaPB treatment, we found that PKC activity was activated rapidly but also decreased rapidly. Down-regulation of PKC-alpha and translocation of PKC-alpha from the cytosol to membrane were seen by Western blot. The decrease in PKC activity by NaPB corresponds to an enhanced response to radiation on CEN2 cells. Moreover, NaPB up-regulated EBV thymidine kinase activity to render EBV-associated Daudi cells susceptible to killing by GCV. Based on the observations of NaPB as a PKC modulator, the combination of NaPB, GCV, and radiation may provide a potential novel approach for treatment of EBV-associated NPC. (+info)