Early virological and immunological events in asymptomatic Epstein-Barr virus infection in African children.

Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection.

Gammaherpesviruses and canine lymphoma: no evidence for direct involvement in commonly occurring lymphomas.

Lymphoma is the most common haematopoietic malignancy in dogs, but little is known about the aetiology of this heterogeneous group of cancers. In humans, the Epstein-Barr virus (EBV) is associated with several lymphoma subtypes. Recently, it was suggested that EBV or an EBV-like virus is circulating in dogs.

Modeling HLA associations with EBV-positive and -negative Hodgkin lymphoma suggests distinct mechanisms in disease pathogenesis.

HLA genotyping and genome wide association studies provide strong evidence for associations between Human Leukocyte Antigen (HLA) alleles and classical Hodgkin lymphoma (cHL). Analysis of these associations is complicated by the extensive linkage disequilibrium within the major histocompatibility region and recent data suggesting that associations with EBV-positive and EBV-negative cHL are largely distinct. To distinguish independent and therefore potentially causal associations from associations confounded by linkage disequilibrium, we applied a variable selection regression modeling procedure to directly typed HLA class I and II genes and selected SNPs from EBV-stratified patient subgroups.

EBV+ diffuse large B-cell lymphoma arising within atrial myxoma. An example of a distinct primary cardiac EBV+ DLBCL of immunocompetent patients.

Cardiac myxoma and diffuse large B-cell lymphoma are uncommon tumors, yet four composite tumors have been reported since 2009. We are reporting on the fifth case providing detailed immunohistochemical and FISH analyses. The lymphoma was present as superficially located nests of large cells with patchy necrosis in the background of a typical atrial myxoma.

Role of the HLA system in the association between multiple sclerosis and infectious mononucleosis.

Objective: To determine whether multiple sclerosis (MS) and infectious mononucleosis (IM) share common HLA associations.

Design: A prospective cohort study was conducted from October 1, 1999, through September 30, 2003.

Setting: University of Edinburgh Richard Verney Health Centre, Edinburgh, Scotland.

Soluble CD30: a serum marker for Epstein-Barr virus-associated lymphoproliferative diseases.

The soluble form of CD30 (sCD30), a member of tumor necrosis factor receptor superfamily, has been used as a marker of disease activity in various lymphomas. Epstein-Barr virus (EBV) is a potent stimulator of CD30 expression. The study aims to evaluate whether sCD30 can be used as a diagnostic marker for EBV-associated infectious mononucleosis (IM) and post-transplant lymphoproliferative disease (PTLD).

Infectious mononucleosis in university students in the United kingdom: evaluation of the clinical features and consequences of the disease.

Background: Infectious mononucleosis (IM) is common among university students. We undertook to analyze the clinical features and sequelae of the disease in a cohort of students at Edinburgh University.

Methods: Consecutive IM case patients were recruited from 2000 through 2002 at the University Health Service after diagnosis of IM.

Cytolytic mechanisms and T-cell receptor Vbeta usage by ex vivo generated Epstein-Barr virus-specific cytotoxic T lymphocytes.

Ex-vivo-generated Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) have been used for cellular adoptive immunotherapy of EBV-associated lymphomas. Here we investigated the phenotypes, cytolytic mechanisms, polyfunctionality and T-cell receptor (TCR) usage in growing and established CTL, generated by weekly stimulation with an EBV-transformed autologous lymphoblastoid cell line (LCL). Our results showed that phenotypically mature CTL developed within the first 4 weeks of culture, with an increase in CD45RO and CD69, and a decrease in CD45RA, CD62L, CD27 and CD28 expression.

Epitope specificity and clonality of EBV-specific CTLs used to treat posttransplant lymphoproliferative disease.

In a recent phase II clinical trial using banked allogeneic CTL lines to treat EBV-associated posttransplant lymphoproliferative disease, a response rate of 52% was recorded 6 mo posttreatment. Tumor response was associated with an increase in both CTL/recipient HLA matches and CD4(+) T cells within the infused CTL lines. The present study was undertaken to correlate tumor response with CTL specificity.

HLA class I polymorphisms are associated with development of infectious mononucleosis upon primary EBV infection.

Infectious mononucleosis (IM) is an immunopathological disease caused by EBV that occurs in young adults and is a risk factor for Hodgkin lymphoma (HL). An association between EBV-positive HL and genetic markers in the HLA class I locus has been identified, indicating that genetic differences in the HLA class I locus may alter disease phenotypes associated with EBV infection. To further determine whether HLA class I alleles may affect development of EBV-associated diseases, we analyzed 2 microsatellite markers and 2 SNPs located near the HLA class I locus in patients with acute IM and in asymptomatic EBV-seropositive and -seronegative individuals.

Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial.

We present the results of a multicenter clinical trial using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) generated from EBV-seropositive blood donors to treat patients with EBV-positive posttransplantation lymphoproliferative disease (PTLD) on the basis of the best HLA match and specific in vitro cytotoxicity. Thirty-three PTLD patients who had failed on conventional therapy were enrolled. No adverse effects of CTL infusions were observed and the response rate (complete or partial) in 33 patients was 64% at 5 weeks and 52% at 6 months.

A study of risk factors for acquisition of Epstein-Barr virus and its subtypes.

Background: Risk factors for primary infection with Epstein-Barr virus (EBV) and its subtypes have not been fully investigated.

Methods: Questionnaires and serum samples from a total of 2006 students who entered Edinburgh University in 1999-2000 were analyzed to examine risk factors for EBV seropositivity, both overall and by EBV type.

Results: The prevalence of EBV seropositivity was significantly increased among females, older students, those who had lived in tropical countries, those with siblings, and those who were sexually active, particularly if they had had numerous sex partners.

Evidence of shared Epstein-Barr viral isolates between sexual partners, and low level EBV in genital secretions.

Epstein-Barr virus is present in the saliva of most persistently infected individuals and is generally thought to be spread by close oral contact. However, there are now several reports of EBV in genital secretions, suggesting the possibility of sexual transmission between adults. The present study was undertaken to investigate the risk of sexual transmission of EBV.

A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis.

Background: A vaccine against Epstein-Barr virus (EBV) infection is in clinical trials. Up-to-date information on risk factors for EBV infection and infectious mononucleosis (IM) among young adults is required to inform a vaccination strategy.

Methods: We carried out a prospective study on a cohort of university students.

Epstein-Barr virus can establish infection in the absence of a classical memory B-cell population.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persists in the body for life after primary infection. The primary site of EBV persistence is the memory B lymphocyte, but whether the virus initially infects naïve or memory B cells is still disputed. We have analyzed EBV infection in nine cases of X-linked hyper-immunoglobulin M (hyper-IgM) syndrome who, due to a mutation in CD40 ligand gene, do not have a classical, class-switched memory B-cell population (IgD(-) CD27(+)).

The immune response to primary EBV infection: a role for natural killer cells.

The role of antigen-specific CD3(+)CD8(+) cytotoxic T cells in the control of primary Epstein-Barr Virus (EBV) infection is well established. However, time is required for the antigen-specific immune response to develop and expand. In contrast, innate immune responses, such as natural killer (NK) cells, are considered vital early in the infection process.

Analysis of immune activation and clinical events in acute infectious mononucleosis.

The symptoms of infectious mononucleosis (IM) are thought to be caused by T cell activation and cytokine production. Surface lymphocyte activation marker (SLAM)-associated protein (SAP) regulates lymphocyte activation via signals from cell-surface CD244 (2B4) and SLAM (CD150). We followed T cell activation via this SAP/SLAM/CD244 pathway in IM and analyzed whether the results were associated with clinical severity.

Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion.

Background & Aims: Studies have indicated that stem cells have unexpected plasticity and can differentiate down a multitude of nonhematopoietic cell lineages in rodents. Our aim was to identify whether human cord blood cells, which are a rich source of stem cells, would be able to differentiate into hepatocytes when infused into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. We also wanted to test whether such differentiated cells were the result of cellular fusion or true stem cell transdifferentiation.

Sexual history and Epstein-Barr virus infection.

To determine the role of sexual contact in transmission of Epstein-Barr virus (EBV) and occurrence of infectious mononucleosis (IM), a cross-sectional study was undertaken of EBV serologic testing and histories of IM and sexual behavior among 1006 new students at Edinburgh University. Prevalence of EBV seropositivity was significantly greater among women (79.2%) than among men (67.