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inhibitory molecules that regulate expansion and restoration of hcv-specific cd4+ t cells in patients with chronic infection.background & aims: inhibitory receptors such as programmed death (pd)-1 and cytotoxic t lymphocyte-associated antigen (ctla)-4 mediate cd8+ t-cell exhaustion during chronic viral infection, but little is known about roles in dysfunction of cd4+ t cells. methods: we investigated the functions of inhibitory molecules on hepatitis c virus (hcv)-, influenza-, and epstein-barr-virus (ebv)-specific cd4+ t cells in patients with chronic infections, compared with patients that resolve hcv infection and ...201121763239
fc?riiia (cd16) induction on human t lymphocytes and cd16pos t-lymphocyte amplification.during serial assays designed to amplify natural killer (nk) cells in vitro, we observed that when peripheral blood mononuclear cells (pbmcs) from human immunodeficiency virus positive (hiv+) patients were stimulated for 2 weeks with an epstein-barr virus-infected b lymphoblastic cell line and interleukin-2, a well known procedure to amplify nk cells in vitro, 44.4±18% cd3cd16 t lymphocytes were recovered together with nk cells, of which 78.2% expressed an aß t-cell receptor (tcr). to identify t ...201121760529
tumor suppressor genes fhit and wwox are deleted in primary effusion lymphoma (pel) cell lines.primary effusion lymphoma (pel) is a diffuse-large b-cell lymphoma with poor prognosis. one hundred percent of pels carry the genome of kaposi sarcoma-associated herpesvirus and a majority are coinfected with epstein-barr virus (ebv). we profiled genomic aberrations in pel cells using the affymetrix 6.0 snp array. this identified for the first time individual genes that are altered in pel cells. eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors wwox and fhit. alterat ...201121685375
autoimmune hepatitis following epstein-barr virus infection.we describe a case of a young man with autoimmune hepatitis (aih) following epstein-barr virus (ebv) infection, in whom a long follow-up showed favourable outcome with complete clinical recovery and failure to relapse after cessation of immunosuppressive therapy. the study underlines the importance of the differential diagnosis between primary ebv associated hepatitis with features of autoimmunity, in which there is a direct pathogenetic role of the virus, and ebv related aih, in which ebv could ...200821716814
cellular transcription factor oct-1 interacts with the epstein-barr virus brlf1 protein to promote disruption of viral latency.the epstein-barr virus (ebv) latent-to-lytic switch is an essential part of the viral life cycle, but the cellular factors that promote viral reactivation are not well defined. in this report, we demonstrate that the cellular transcription factor oct-1 cooperates with the ebv immediate-early protein brlf1 (r, rta) to induce lytic viral reactivation. we show that cotransfected oct-1 enhances the ability of brlf1 to activate lytic gene expression in 293 cells stably infected with a brlf1-defective ...201121697476
microorganisms and valve tissue/ demonstration of chlamydophila pneumoniae, mycoplasma pneumoniae, cytomegalovirus, and epstein-barr virus in atherosclerotic coronary arteries, nonrheumatic calcific aortic and rheumatic stenotic mitral valves by polymerase chain reaction. 201121827993
lymphoepithelial carcinoma: two case reports and a systematic review of oral and sinonasal cases.lymphoepithelial carcinoma (lec) is a rare malignancy. histologically, it is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. herein, we report two cases of lec in the head and neck region that presented to oulu university hospital. our first case is a 30-year-old man with lec in the left maxillary sinus. the second case is a 49-year-old man with lec in the soft palate and uvula with regional lymph node metastases at diagnosis. in addition, a systematic rev ...201121698444
oncogenic irfs provide a survival advantage for epstein-barr virus- or human t-cell leukemia virus type 1-transformed cells through induction of bic expression.mir-155, processed from the b-cell integration cluster (bic), is one of the few well-studied micrornas (mirnas) and is involved in both innate immunity and tumorigenesis. bic/mir-155 is induced by distinct signaling pathways, but little is known about the underlying mechanisms. we have identified two conserved potential interferon (ifn) regulatory factor (irf)-binding/interferon-stimulated response element motifs in the bic gene promoter. two oncogenic irfs, irf4 and -7, in addition to some othe ...201121680528
a "silent" nucleotide substitution in exon 4 is responsible for the "alternative expression" of hla-a*01:01:38l through aberrant splicing.a welsh bone marrow donor registry donor was serologically typed, using both alloantisera and monoclonal antibodies, as human leukocyte antigen (hla)-a2, a-, but typed by polymerase chain reaction sequence-specific priming as hla-a*01, a*02. full gene sequencing of the a*01 separated allele indicated an apparently normal a*01:01:01:01 apart from a silent change at nucleotide 705 in exon 4, codon 211 (alanine: normally gcg but gca in this donor). sequence analysis of the amplified a*01 allele in ...201121741421
human immunoglobulin g levels of viruses and associated glioma risk.few consistent etiological factors have been identified for primary brain tumors. inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large scandinavian cohorts. to test the hypothesis that immu ...201121717196
herpesvirus carriage in saliva and posttreatment apical periodontitis: searching for association.objective: herpesvirus infection can cause immunosuppression and then act as a modifier of apical periodontitis, influencing the disease severity and response to treatment. the purpose of this study was to investigate if herpesvirus infection, as inferred by salivary carriage, may influence the endodontic treatment outcome. study design: the study population included 72 patients who had root canals treated more than 1 year previously because of necrotic pulps and apical periodontitis. at the fol ...201121831677
epstein-barr virus and multiple sclerosis.this review of the considerable evidence linking epstein-barr virus (ebv) infection to risk and disease progression in multiple sclerosis (ms) builds on the background to the virus and its interactions with the human host available in the online supplement (see supplement, available online only). the evidence for a similarity in the geographic patterns of occurrence of ms and ebv infection (with infectious mononucleosis or ebv specific serology used as surrogate markers), when reviewed criticall ...201121836034
[interstitial kidney injury due to viral infection]. 201121688483
the np9 protein encoded by the human endogenous retrovirus herv-k(hml-2) negatively regulates gene activation of the epstein-barr virus nuclear antigen 2 (ebna2).epstein-barr virus (ebv) is a human tumour virus that efficiently growth-transforms primary human b-lymphocytes in vitro. the viral nuclear antigen 2 (ebna2) is essential for immortalisation of b-cells and stimulates viral and cellular gene expression through interaction with dna-bound transcription factors. like its cellular homologue notch, it associates with the dna-bound repressor rbpj+¦ (csl/cbf1) thereby converting rbpj+¦ into the active state. for instance, both ebna2 and notch activate t ...201121710493
t7 phage displaying latent membrane protein 1 of epstein-barr virus elicits humoral and cellular immune responses in rats.the latent membrane protein 1 (lmp1) encoded by epstein-barr virus (ebv) has become a potential target in ebv-associated tumor prevention and treatment due to its multiple biological effects. in this study, the recombinant t7 phage displaying full-length lmp1 protein was cloned and used as an immunogen to immunize rats. results of flow cytometry, western blot analysis, and elisa confirmed that both humoral and cellular immune responses were elicited in the immunized rats. our data suggested that ...201121692559
adoptive immunotherapy with virus-specific t cells.viral infections are still common causes of morbidity and mortality in immunosuppressed patients after allogeneic hematopoietic stem cell transplantation. infections caused by virus such as cytomegalovirus, adenovirus and epstein-barr virus are well-known. in addition, several other viruses such as polyomavirus and human herpesvirus 6 have been recently reported to be causes of significant complications. as the delay in recovery of virus-specific cellular immune response after transplant is asso ...201121925094
Discrepancy in EBV-DNA load between peripheral blood and cerebrospinal fluid in a patient with isolated CNS post-transplant lymphoproliferative disorder.Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is caused by reactivation of Epstein-Barr virus (EBV). A successful approach, monitoring EBV-DNA load in peripheral blood (PB) accompanied by preemptive rituximab therapy, has recently been reported. Here, we describe a 29-year-old woman who developed isolated central nervous system (CNS) PTLD. She received HSCT against acute myelogenous leukemia from a re ...201122038015
clinical characteristics of patients with epstein barr virus in cerebrospinal fluid.the role of epstein-barr (ebv) virus in central nervous system (cns) infections is not fully resolved. it is clearly associated with lymphoproliferative disease of immunosuppressed persons, and may cause encephalitis.201122018204
syk activation of phosphatidylinositol 3-kinase/akt prevents htra2-dependent loss of x-linked inhibitor of apoptosis protein (xiap) to promote survival of epstein-barr virus+ (ebv+) b cell lymphomas.b cell lymphoma survival requires tonic or ligand-independent signals through activation of syk by the b cell receptor. the epstein-barr virus (ebv) protein latent membrane 2a (lmp2a), a mimic of the b cell receptor, provides constitutive survival signals for latently infected cells through syk activation; however, the precise downstream mechanisms coordinating this survival response in ebv+ b cell lymphomas remain to be elucidated. herein, we assess the mechanism of syk survival signaling in eb ...201121908615
comparison of humoral immune responses to epstein-barr virus and kaposi's sarcoma-associated herpesvirus using a viral proteome microarray.epstein-barr virus (ebv) is a ubiquitous herpesvirus, and kaposi's sarcoma-associated herpesvirus (kshv) has a restricted seroprevalence. both viruses are associated with malignancies that have an increased frequency in individuals who are coinfected with human immunodeficiency virus type 1 (hiv-1).201121990424
Understanding TLR9 action in Epstein-Barr virus infection.The Epstein-Barr virus (EBV) establishes persistent latent infection in peripheral blood memory B cells, may cause infectious mononucleosis, and is associated with cancers including endemic Burkitt's lymphoma (BL). Although latent EBV transforms B cells in vitro, additional factors including immunocompromised status or, as in endemic BL, a co-infection with the malaria parasite Plasmodium falciparum seem to be required for the development of EBV-associated cancers. Toll-like receptors (TLRs) lik ...201222201799
epstein-barr virus latent membrane protein 1 induces cancer stem/progenitor-like cells in nasopharyngeal epithelial cell lines.recent studies suggest the existence of cancer stem cells (csc) and cancer progenitor cells (cpc), although strict definitions of neither csc nor cpc have been developed. we have produced evidence that the principal oncoprotein of epstein-barr virus (ebv), latent membrane protein 1 (lmp1), which is associated with human malignancies, especially nasopharyngeal carcinoma (npc), promotes tumor cell invasion and metastasis, as well as the epithelial-mesenchymal transition (emt). however, whether lmp ...201121849440
application of a novel highly sensitive activity-based probe for detection of cathepsin g.cathepsins are crucial in antigen processing in the major histocompatibility complex class ii (mhc ii) pathway. within the proteolytic machinery, three classes of proteases (i.e., cysteine, aspartic, and serine proteases) are present in the endocytic compartments. the combined action of these proteases generates antigenic peptides from antigens, which are loaded to mhc ii molecules for cd4(+) t cell presentation. detection of active serine proteases in primary human antigen-presenting cells (apc ...201122178917
a critical role for stat3 transcription factor signaling in the development and maintenance of human t cell memory.stat3 transcription factor signaling in specific t helper cell differentiation has been well described, although the broader roles for stat3 in lymphocyte memory are less clear. patients with autosomal-dominant hyper-ige syndrome (ad-hies) carry dominant-negative stat3 mutations and are susceptible to a variety of bacterial and fungal infections. we found that ad-hies patients have a cell-intrinsic defect in the number of central memory cd4(+) and cd8(+) t cells compared to healthy controls. nai ...201122118528
real-time pcr detection of human herpesvirus 1-5 in patients lacking clinical signs of a viral cns infection.infections of the central nervous system (cns) with herpes- or enterovirus can be self-limiting and benign, but occasionally result in severe and fatal disease. the polymerase chain reaction (pcr) has revolutionized the diagnostics of viral pathogens, and by multiple displacement amplification (mda) prior to real-time pcr the sensitivity might be further enhanced. the aim of this study was to investigate if herpes- or enterovirus can be detected in cerebrospinal fluid (csf) from patients without ...201121849074
genetic factors influence serological measures of common infections.antibodies against infectious pathogens provide information on past or present exposure to infectious agents. while host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. here we test whether antibody levels for 13 common infections are significantly heritable.201121996708
comparison of qiasymphony automated and qiaamp manual dna extraction systems for measuring epstein-barr virus dna load in whole blood using real-time pcr.automated and manual extraction systems have been used with real-time pcr for quantification of epstein-barr virus [human herpesvirus 4 (hhv-4)] dna in whole blood, but few studies have evaluated relative performances. in the present study, the automated qiasymphony and manual qiaamp extraction systems (qiagen, valencia, ca) were assessed using paired aliquots derived from clinical whole-blood specimens and an in-house, real-time pcr assay. the detection limits using the qiasymphony and qiaamp s ...201121889612
The lytic phase of epstein-barr virus requires a viral genome with 5-methylcytosine residues in CpG sites.Epstein-Barr virus (EBV) is a human herpesvirus which has been studied intensively for its role in certain human tumors. It also serves as a model of herpesviral latency because it establishes an immediate, latent infection in human B cells. When EBV infects quiescent, primary B cells it induces their continuous proliferation to yield growth-transformed B-cell lines in vitro. The lytic or productive phase of EBV's life cycle is induced by the expression of the viral BZLF1 gene in latently infect ...201222031942
oral hairy leukoplakia. 201122128498
[lymphomatoid granulomatosis revealed by cutaneous lesions].lymphomatoid granulomatosis is a rare epstein barr virus (ebv)-related lymphoproliferative disorder. it most frequently involves the lungs, skin and central nervous system and arises preferentially in patients with immune disorders. here we report a case revealed by cutaneous lesions in an immunocompetent patient.201121893233
identification of the distinctive type i/xhoi+ strain of epstein-barr virus in gastric carcinoma in peru.to clarify the reason for the low frequency of epstein-barr virus-associated gastric carcinoma (ebvagc) in peru, despite the high frequency reported in neighboring countries, the distribution of the distinctive ebv (type i/xhoi+) strain in ebvagc and a healthy population was examined.201121965785
Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in malawian adults with bacterial meningitis.Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that-particularly in individuals infected with human immunodeficiency virus (HIV)-herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis ...201222075766
Poly(ADP-ribose) polymerase inhibitors combined with external beam and radioimmunotherapy to treat aggressive lymphoma.To assess the possible radiosensitizing capabilities of two different poly(ADP-ribose) polymerase (PARP) inhibitors in combination with external beam and I-tositumomab in a non-Hodgkin's lymphoma cell line.201121956491
exhausted cytotoxic control of epstein-barr virus in human lupus.systemic lupus erythematosus (sle) pathology has long been associated with an increased epstein-barr virus (ebv) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. it has therefore been postulated that ebv triggers sle immunopathology, although the mechanism remains elusive. here, we investigate whether frequent peaks of ebv viral load in sle patients are a consequence of dysfunctional anti-ebv cd8+ t cell responses. both inactive and active sle patient ...201122028659
development of the hybrid sleeping beauty-baculovirus vector for sustained gene expression and cancer therapy.antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. baculovirus is an emerging gene delivery vector but only mediates transient expression (<7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. we first constructed plasmids featuring adeno-associated virus inverted terminal repeats (aav itrs), orip/epstein-barr ...201121918552
The company malaria keeps: how co-infection with Epstein-Barr virus leads to endemic Burkitt lymphoma.Co-infection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) are implicated in the cause of endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in equatorial Africa. Although the causal association between EBV and eBL has been established, P. falciparum malaria's role is not as clearly defined. This review focuses on how malaria may disrupt EBV persistence and immunity.201121885920
Classification of epstein-barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.Epstein-Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has not been fully clarified. We analyzed promoter methylation in gastric cancer cases with Illumina's Infinium BeadArray and used hierarchical clustering analysis to classify gastric ca ...201121990320
Persistent infection drives the development of CD8+ T cells specific for late lytic infection antigens in lymphocryptovirus-infected macaques and Epstein-Barr virus-infected humans.We examined the CD8(+) T cell repertoire against lytic infection antigens in rhesus macaques persistently infected with the Epstein-Barr virus (EBV)-related lymphocryptovirus (rhLCV). CD8(+) T cells specific for late (L) antigens were detected at rates comparable to those for early antigens and were associated with increasing duration of infection. L antigen-specific CD8(+) T cells were also readily detected in adult, EBV-positive humans. Thus, viral major histocompatibility complex class I (MHC ...201121917961
[T-cell large granular lymphocyte leukemia after autologous peripheral blood stem cell transplantation for malignant lymphoma-report of three cases and a review of the literature].There have been only three reports in the literature of T-cell large granular lymphocyte (T-LGL) leukemia occurring after autologous peripheral stem cell transplantation (APBSCT). We describe 3 patients in whom a transient monoclonal T-LGL developed after APBSCT for malignant lymphoma. Case 1: A 58-year-old man with peripheral T-cell lymphoma in second complete remission (CR) who underwent APBSCT. Case 2: A 51-year-old man with follicular lymphoma in second CR who underwent APBSCT. Case 3: A 65- ...201121996977
Peripheral T-cell lymphoma arising from an intraglandular lymph node in the parotid gland: A case report and literature review.T/NK-cell lymphoma of the salivary gland is rare. A 58-year-old man complained of a tumor mass in the left parotid gland region and he was diagnosed to have a left parotid tumor. The tumor was subsequently resected, revealing a diffuse growth pattern of medium to large sized atypical cells. The tumor was surrounded by fibrous connective tissue in the form of a capsule, and those were positive for CD3, CD4, CD5 and CD30, but negative for Bcl2, CD8, CD10, CD15, CD20, CD25, CD56, CD79a, CD246, EMA, ...201222192806
Latent membrane protein 1 is dispensable for Epstein-Barr virus replication in human embryonic kidney 293 cells.Epstein Barr Virus (EBV) replicates in oral epithelial cells and gains entry to B-lymphocytes. In B-lymphocytes, EBV expresses a restricted subset of genes, the Latency III program, which converts B-lymphocytes to proliferating lymphoblasts. Latent Membrane Protein 1 (LMP1) and the other Latency III associated proteins are also expressed during virus replication. LMP1 is essential for virus replication and egress from Akata Burkitt Lymphoma cells, but a role in epithelial cell replication has no ...201121853056
Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients.Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only.201121892950
guillain-barre syndrome presenting with sensory disturbance following a herpes virus infection: a case report.abstract: introduction: we present a case of an unusual clinical manifestation of guillain-barre syndrome following a pre-existing herpes virus infection. although there have been several reports describing the co-existence of herpes virus infection and guillain-barre syndrome, we undertook a more in-depth study of the cross-reactivity between herpes viruses and recommend a follow-up study based on serology tests. case presentation: a 39-year-old healthy caucasian man with guillain-barre syndro ...201122136568
Cytotoxic T Lymphocytes Simultaneously Targeting Multiple Tumor-associated Antigens to Treat EBV Negative Lymphoma.Although immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) can treat EBV-associated Hodgkin and non-Hodgkin lymphoma (HL/NHL), more than 50% of such tumors are EBV negative. We now describe an approach that allows us to consistently generate, in a single line, CTLs that recognize a wide spectrum of nonviral tumor-associated antigens (TAAs) expressed by human HL/NHL, including Survivin, MAGE-A4, Synovial sarcoma X (SSX2), preferentially expressed antigen in melan ...201121915103
posttransplant lymphoproliferative disorder presenting as multiple cystic lesions in a renal transplant recipient.we report a case of a 67-year-old man who experienced allograft dysfunction following a renal transplantation from a donation after cardiac death. the postoperative course was initially complicated by episodes of e. coli urinary sepsis causing pyrexia and a raised creatinine level. ultrasound scanning 5 weeks posttransplant revealed mild hydronephrosis with several parenchymal cystic areas measuring up to 2 cm with appearances suggestive of fungal balls. aspirated fluid again grew escherichia co ...201222244123
inhibition of the latent membrane protein-1 impairs the growth and tumorigenesis of an ebv-latency ii transformed t-cell.the epstein-barr virus (ebv) is a common human herpes virus. its infection is associated with several human malignancies where it expresses a set of latent proteins among which is the latent membrane protein lmp1. lmp1 is able to transform numerous cell types and is considered the main oncogenic protein of ebv. the mechanism of action is based on mimicry to activated members of the tnf receptor superfamily, through its ability to bind similar adapters and to activate signaling pathways. we previ ...201222258264
in vitro and in vivo antitumor effect of anti-cd33 chimeric receptor-expressing ebv-ctl against cd33 acute myeloid leukemia.genetic engineering of t cells with chimeric t-cell receptors (cars) is an attractive strategy to treat malignancies. it extends the range of antigens for adoptive t-cell immunotherapy, and major mechanisms of tumor escape are bypassed. with this strategy we redirected immune responses towards the cd33 antigen to target acute myeloid leukemia. to improve in vivo t-cell persistence, we modified human epstein barr virus-(ebv-) specific cytotoxic t cells with an anti-cd33.car. genetically modified ...201222272203
host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
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