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low intrathecal antibody production despite high seroprevalence of epstein-barr virus in multiple sclerosis: a review of the literature.patients with multiple sclerosis (ms) frequently have an intrathecal production of antibodies to different common viruses, which can be detected by elevated antiviral antibody indices (ais). there is a strong and consistent association of ms and epstein-barr virus (ebv) infection.201729098417
autophagy proteins in phagocyte endocytosis and exocytosis.autophagy was initially described as a catabolic pathway that recycles nutrients of cytoplasmic constituents after lysosomal degradation during starvation. since the immune system monitors products of lysosomal degradation via major histocompatibility complex (mhc) class ii restricted antigen presentation, autophagy was found to process intracellular antigens for display on mhc class ii molecules. in recent years, however, it has become apparent that the molecular machinery of autophagy serves p ...201729018446
monoclonal igg in mgus and multiple myeloma targets infectious pathogens.subsets of mature b cell neoplasms are linked to infection with intracellular pathogens such as epstein-barr virus (ebv), hepatitis c virus (hcv), or helicobacter pylori. however, the association between infection and the immunoglobulin-secreting (ig-secreting) b proliferative disorders remains largely unresolved. we investigated whether the monoclonal igg (mc igg) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (mgus) or multiple myeloma (mm) targets infec ...201728978808
intraocular detection of herpesviruses by xtag liquid chip technology in patients with acute retinal necrosis.to evaluate the performance of the xtag liquid chip technology (xtag-lct) for etiological diagnosis of acute retinal necrosis (arn).201728960122
[infectious mononucleosis and cholestatic hepatitis: a rare association].infectious mononucleosis is one of the major clinical manifestations of epstein-barr virus infection. in this syndrome, elevation of liver transaminase levels is common but cholestasis is rare, with few cases described in the literature. we present the case of a 14-year-old female adolescent, admitted to the emergency room with fever, odynophagia and cervical adenomegaly. she was treated with amoxicillin and two days later he presented with jaundice. the analytical evaluation was compatible with ...201729364802
toll-like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?pathogen infections and dysregulated toll-like receptor (tlr)-mediated innate immune responses are suspected to play key roles in autoimmunity. among tlrs, tlr7 and tlr9 have been implicated in several autoimmune conditions, mainly because of their ability to promote abnormal b cell activation and survival. recently, we provided evidence of epstein-barr virus (ebv) persistence and reactivation in the thymus of myasthenia gravis (mg) patients, suggesting an involvement of ebv in the intrathymic p ...201829363775
no increased risk of posttransplant lymphoproliferative disorder following alemtuzumab induction in kidney transplant.posttransplant lymphoproliferative disorder is a known complication of solid-organ transplant. the use of depleting induction agents has demonstrated varying associations with incidence of posttransplant lymphoproliferative disorder. alemtuzumab, a depleting induction agent for kidney transplant patients, has shown promising results in reducing the risk of acute rejection and graft loss in the first year. its unique mechanism of depleting both t-cell and b-cell populations may be beneficial in p ...201829363415
expression of activating nk-cell receptors is a hallmark of the innate-like t-cell neoplasm in peripheral t-cell lymphomas.peripheral t- or nk-cell lymphomas are rare and difficult-to-recognize diseases. it remains arduous to distinguish between nk cell- and cytotoxic t lymphocyte-derived lymphomas through routine histologic evaluation. to clarify the cells of origin, we focused on nk-cell receptors and examined the expression using immunohistochemistry in 22 cases with t- and nk-cell neoplasms comprising of angioimmunoblastic t-cell lymphoma, alk-positive and -negative anaplastic large cell lymphomas, extranodal nk ...201829363227
mutation analysis of the ebv-lymphoblastoid cell line cautions their use as antigen-presenting cells.lymphoblastoid cell lines (lcls) have been widely used as professional antigen-presenting cells (apcs). however, neoantigen-loaded lcls could induce nonspecific t-cell response, which could be due to expression of both epstein-barr virus (ebv) antigens and nonsynonymous mutations arising in lcls. since the number of passages could influence mutational characteristics of lcls, and moreover extensive proliferation of lcls in vitro is necessary to activate t cells for immunotherapy, we comprehensiv ...201729363169
human mhc-ii with shared epitope motifs are optimal epstein-barr virus glycoprotein 42 ligands-relation to rheumatoid arthritis.rheumatoid arthritis (ra) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. although the pathogenesis of ra remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. especially genetic factors play a vital role in the onset of disease, as the heritability of ra is 50-60%, with the human leukocyte antigen (hla) alleles accounting for at least 3 ...201829361739
[a case of cervical lymph node metastasis from an unknown primary cancer controlled with immunotherapy, chemotherapy, and surgery].we present a case of cervical lymph node metastasis from an unknown primary cancer that was controlled with immunotherapy, chemotherapy, and surgery. the patient, a 61-year-old man, was referred to our department for treatment of a lesion in the left cervical lateral area. at the initial visit, the mass was covered by reddened skin and was elastic, hard, and immobile on palpation. the presence of a malignant disease such as malignant lymphoma or lymphadenitis because of infection by tubercle bac ...201729361629
a novel epstein-barr virus-latent membrane protein-1-specific t-cell receptor for tcr gene therapy.adoptive transfer of genetically engineered t-cells to express antigen-specific t-cell receptor (tcr) is a feasible and effective therapeutic approach for numerous types of cancers, including epstein-barr virus (ebv)-associated malignancies. here, we describe a tcr gene transfer regimen to rapidly and reliably generate t-cells specific to ebv-encoded latent membrane protein-1 (lmp1), which is a potential target for t-cell-based immunotherapy.201829360818
long-term follow up of post renal transplantation epstein-barr virus-associated smooth muscle tumors: report of two cases and review of the literature.epstein-barr virus (ebv)-associated smooth muscle tumors (smts) following solid organ transplantation are very rare slow growing neoplasms. most tumors present with non-specific symptoms mainly related to tumor location. post-transplant ebv-associated small muscle tumors have been reported in various anatomical locations. the tumors have a predilection to unusual sites for smts and tend to be multifocal. the histologic appearance of these tumors generally does not predict their clinical behavior ...201829359839
epstein-barr virus and hemophagocytic lymphohistiocytosis.epstein-barr virus (ebv) is a ubiquitous virus that infects nearly all people worldwide without serious sequela. however, for patients who have genetic diseases which predispose them to the development of hemophagocytic lymphohistiocytosis (hlh), ebv infection is a life-threatening problem. as a part of a themed collection of articles on ebv infection and human primary immune deficiencies, we will review key concepts related to the understanding and treatment of hlh.201729358936
herpesvirus deconjugases inhibit the ifn response by promoting trim25 autoubiquitination and functional inactivation of the rig-i signalosome.the n-terminal domains of the herpesvirus large tegument proteins encode a conserved cysteine protease with ubiquitin- and nedd8-specific deconjugase activity. the proteins are expressed during the productive virus cycle and are incorporated into infectious virus particles, being delivered to the target cells upon primary infection. members of this viral enzyme family were shown to regulate different aspects of the virus life cycle and the innate anti-viral response. however, only few substrates ...201829357390
interferon regulatory factor 8 regulates aspase-1 expression to facilitate epstein-barr virus reactivation in response to b cell receptor stimulation and chemical induction.interferon regulatory factor 8 (irf8), also known as interferon consensus sequence-binding protein (icsbp), is a transcription factor of the irf family. irf8 plays a key role in normal b cell differentiation, a cellular process that is intrinsically associated with epstein-barr virus (ebv) reactivation. however, whether irf8 regulates ebv lytic replication remains unknown. in this study, we utilized a crispr/cas9 genomic editing approach to deplete irf8 and found that irf8 depletion dramatically ...201829357389
association of cytomegalovirus and epstein-barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study.earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. few studies have investigated the association of cytomegalovirus and epstein-barr virus with cognitive decline longitudinally. our aim was to examine whether cytomegalovirus and epstein-barr virus are associated with cognitive decline in adults method: the study sample is from the finnish health 2000 survey (brif8901, n = 7112), which is representative of the finni ...201829355820
characterization of skin blister fluids from children with epstein-barr virus-associated lymphoproliferative disease.epstein-barr virus (ebv)-associated t- or natural killer (nk)-cell lymphoproliferative disease (lpd) is a heterogeneous group of disorders characterized by chronic proliferation of ebv-infected lymphocytes. patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (hmb) and hydroa vacciniforme (hv)-like eruption, which are characterized by blister formation and necrotic ulceration. skin biopsy specimens show inflammatory reactions comprising ebv-infected ...201829352500
current perspectives on erythema multiforme.recognition and timely adequate treatment of erythema multiforme remain a major challenge. in this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. the diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histologic ...201829352387
epstein-barr virus encoded latent membrane protein 1 suppresses necroptosis through targeting ripk1/3 ubiquitination.necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (ripk1) and ripk3. this form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. however, only a few viral species such as herpes simplex virus (hsv) and cytomegalovirus (cmv) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, ...201829352166
membranoproliferative glomerulonephritis and interstitial nephritis in the setting of epstein-barr virus-related hemophagocytic syndrome
.hemophagocytic syndrome (hps) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. less frequently, glomerulopathy can also be found.201829350173
elevated levels of interferon-γ are associated with high levels of epstein-barr virus reactivation in patients with the intestinal type of gastric cancer.the inflammatory response directed against helicobacter pylori (hp) is believed to be one of the main triggers of the appearance of gastric lesions and their progression to gastric cancer (gc). epstein-barr virus (ebv) has been found responsible for about 10% of all gcs, but the inflammatory response has not been studied in gc patients with evidence of high levels of ebv reactivation.201729349089
microsatellite stability and mismatch repair proficiency in nasopharyngeal carcinoma may not predict programmed death-1 blockade resistance.the us fda granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. the response of programmed death-1 blockade in mismatch repair proficiency (pmmr) colorectal cancer is very poor, however, whether such treatment is effective in pmmr nasopharyngeal carcinoma (npc) remains unknown. we report a case of a 51-year-old man with npc. pet-ct scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the o ...201729348907
therapeutic manipulation of host cell death pathways to facilitate clearance of persistent viral infections.most persistent viral infections can be controlled, but not cured, by current therapies. abrogated antiviral immunity and stable latently infected cells represent major barriers to cure. this necessitates life-long suppressive antiviral therapy. achieving a cure for hiv, hepatitis b virus, epstein barr-virus, and others, requires novel approaches to facilitate the clearance of infected cells from the host. one such approach is to target host cell death pathways, rather than the virus itself. her ...201829345371
orbital epstein-barr virus-positive polymorphic b-cell lymphoproliferative disorder in an apparently immunocompetent woman.we report a rare case of epstein-barr virus (ebv)-positive polymorphic b-cell lymphoproliferative disorder (lpd) involving the lacrimal gland of a 28-year-old, apparently immunocompetent woman. she presented with a chief complaint of orbital swelling and tenderness and was found to have a lesion involving the right lacrimal gland and distal superior and lateral rectus muscles. histology of the lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and scattered cells that res ...201729344502
gamma-herpesvirus colonization of the spleen requires lytic replication in b cells.gamma-herpesviruses infect lymphocytes and cause lymphocytic cancers. murid herpesvirus-4 (muhv-4), epstein-barr virus and the kaposi's sarcoma-associated herpesvirus all infect b cells. latent infection can spread by b cell recirculation and proliferation, but whether this alone achieves systemic infection is unclear. to test the need of muhv-4 for lytic infection in b cells we flanked its essential orf50 lytic transactivator with loxp sites, then infected mice with b cell-specific cre expressi ...201829343572
[x-linked immunodeficiency with magnesium defect, epstein-barr virus infection, and neoplasia: report of a family and literature review].objective: to investigate the clinical features and genetic characteristics of cases with x-linked immunodeficiency with magnesium defect, epstein-barr virus (ebv) infection, and neoplasia (xmen). methods: characteristics of clinical material, immunological data and gene mutation of two cases with xmen in the same family in china were retrospectively analyzed. the related reports literature were searched by using search terms'magt1 gene'or'xmen'. results: the proband, a 2-year-eight-month old bo ...201829342998
incidence and predictors of post-transplant lymphoproliferative disease after kidney transplantation during adulthood and childhood: a registry study.differences in the epidemiology of post-transplant lymphoproliferative disease (ptld) between adult and paediatric kidney transplant recipients remain unclear.201829342279
what is the impact of epstein-barr virus in peri-implant infection?to compare the qualitative and quantitative profile of epstein-barr virus (ebv) at external and internal implant surfaces between participants with peri-implantitis and healthy peri-implant tissues and to quantitatively assess the relation between ebv and periopathogens inside the microbiologic profile associated with peri-implantitis.201829340343
transcriptional profile and epstein-barr virus infection status of laser-cut immune infiltrates from the brain of patients with progressive multiple sclerosis.it is debated whether multiple sclerosis (ms) might result from an immunopathological response toward an active epstein-barr virus (ebv) infection brought into the central nervous system (cns) by immigrating b cells. based on this model, a relationship should exist between the local immune milieu and ebv infection status in the ms brain. to test this hypothesis, we analyzed expression of viral and cellular genes in brain-infiltrating immune cells.201829338732
epstein-barr virus infection and type i interferon signature in patients with systemic lupus erythematosus.epstein-barr (eb) virus infection has long been speculated to evoke systemic lupus erythematosus (sle). since a virus infection can induce interferon (ifn) system activation, we aimed to discover the relationship between the two in the progression of sle in a chinese inpatient cohort. methods peripheral blood mononuclear cells and sera were isolated from 116 sle patients and 76 healthy controls. antibodies against ebv-vca (igm and igg) and ebna (igg) along with ifnα in patient sera were detected ...201829338588
crispr/cas9-mediated genome editing in epstein-barr virus-transformed lymphoblastoid b-cell lines.epstein-barr virus (ebv) efficiently transforms primary human b cells into immortalized lymphoblastoid cell lines (lcls), which are extensively used in human genetic, immunological and virological studies. lcls provide unlimited sources of dna for genetic investigation, but can be difficult to manipulate, for instance because low retroviral or lentiviral transduction frequencies hinder experiments that require co-expression of multiple components. this unit details clustered regularly interspace ...201829337376
modulating gene expression in epstein-barr virus (ebv)-positive b cell lines with crispra and crispri.epstein-barr virus (ebv) transforms small resting primary b cells into large lymphoblastoid cells which are able to grow and survive in vitro indefinitely. these cells represent a model for oncogenesis. in this unit, variants of conventional clustered regularly interspaced short palindromic repeats (crispr), namely the crispr activation (crispra) and crispr interference (crispri) methods, are discussed in the context of gene regulation at genomic dna promoter and enhancer elements. lymphoblastoi ...201829337370
epstein barr virus and invasive mammary carcinomas: ebna, ebers and molecular profile in a population of west algeria.breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. a possible viral etiology for breast cancer has been proposed and epstein-barr virus (ebv) is a widely studied candidate virus. the objective of this study is to determine the association of ebv infection with infiltrating ductal carcinomas (idc). this descriptive study was carried out in the laboratory of developmental biology and differentiation ...201829336321
the predictive value of pre- and post-induction chemotherapy plasma ebv dna level and tumor volume for the radiosensitivity of locally advanced nasopharyngeal carcinoma.this study was dedicated to investigate the predictive value of pre- and post-induction chemotherapy plasma ebv (epstein-barr virus) dna level and tumor volume for the radiosensitivity of locally advanced npc. 129 previously untreated locally advanced npc patients were enrolled. plasma ebv-dna copy number and tumor volume was detected before and after induction chemotherapy. the tumor volume was also measured after radiotherapy. among 129 patients, 98 were positive for ebv dna. the residual gros ...201729333129
human papilloma virus-specific t cells can be generated from naïve t cells for use as an immunotherapeutic strategy for immunocompromised patients.human papilloma virus (hpv) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. although treatments exist for hpv-associated malignancies, patients unresponsive to these therapies have a poor prognosis. recent findings from vaccine studies suggest that t-cell immunity is essential for disease control. because epstein-barr virus (ebv)-specific t cells have been highly successful in treating or preventing ebv-associated tumors, we hypothesized that the development of ...201829331266
mutations in pi3k110δ cause impaired nk cell function partially rescued by rapamycin treatment.heterozygous gain-of-function mutations in pi3k110 lead to lymphadenopathy, lymphoid hyperplasia, epstein-barr virus (ebv) and cytomegalovirus (cmv) viremia, and sinopulmonary infections.201829330011
the interactome of ebv lmp1 evaluated by proximity-based bioid approach.epstein-barr virus lmp1 is an oncoprotein required for immortalizing b lymphocytes and also plays important roles in transforming non-lymphoid tissue. the discovery of lmp1 protein interactions will likely generate targets to treat ebv-associated cancers. here, we define the broader lmp1 interactome using the recently developed bioid method. combined with mass spectrometry, we identified over 1000 proteins across seven independent experiments with direct or indirect relationships to lmp1. pathwa ...201829329079
dna methylation enzyme inhibitor rg108 suppresses the radioresistance of esophageal cancer.esophageal cancer (ec) is the eighth most common highly aggressive cancer worldwide. the purpose of this study was to investigate the effect of the dna methyltransferase inhibitor rg108 on the radiosensitivity of ec cells. mtt and clonogenic assays were performed to assess the effect of rg108 on the proliferation and radiosensitivity of eca‑109 and te‑1 human ec cells. the cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. for the in vivo analysis, the eca‑109 c ...201829328411
considerations in the diagnosis of oral hairy leukoplakia-an institutional experience.we report here the 10-year experience with oral hairy leukoplakia (ohl) at the division of oral and maxillofacial pathology at the university of north carolina at chapel hill, nc, usa.201729325854
[opportunistic infection in systemic lupus erythematosus patients: the disease spectrum and the characteristics of peripheral lymphocyte subsets].objective: to investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (sle). methods: from december 2013 to december 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated sle patients with or without opportunistic infections (ois) . the lymphocyte subsets in healthy donors were used as normal control group. results: a total of 145 treated sle patients were enrolle ...201829325308
epstein-barr virus (ebv)-induced b-cell lymphoproliferative disorder mimicking the recurrence of ebv-associated hemophagocytic lymphohistiocytosis.we describe the case of a 23-month-old male infant with epstein-barr virus (ebv)-associated lymphoproliferative disorder, which mimicked the recurrence of ebv-associated hemophagocytic lymphohistiocytosis. chemotherapy with dexamethasone, etoposide, and cyclosporine resolved fever, hepatosplenomegaly, and pancytopenia. however, on day 81 of illness, the patient developed similar symptoms. plasma ebv-dna levels markedly increased again, but no t-cell clonality was observed. b cells were identifie ...201829324572
epstein-barr virus-encoded rnas (ebers) complement the loss of herpesvirus telomerase rna (vtr) in virus-induced tumor formation.marek's disease virus (mdv) is an alphaherpesvirus that causes fatal lymphomas in chickens and is used as a natural virus-host model for herpesvirus-induced tumorigenesis. mdv encodes a telomerase rna subunit (vtr) that is crucial for efficient mdv-induced lymphoma formation; however, the mechanism is not completely understood. similarly, epstein barr-virus (ebv) encodes two rnas (eber-1 and eber-2) that are highly expressed in ebv-induced tumor cells, however their role in tumorigenesis remains ...201829317752
hodgkin's lymphoma and its association with ebv and hiv infection.hodgkin's lymphoma (hl) constitutes a clonal expansion of what appears to be malignant b cells. viruses are involved in its pathogenesis, such as the epstein-barr virus (ebv) and human immunodeficiency virus (hiv). since these viral infections have been shown to play key roles in the pathogenesis of hl, countries with a prevalence of hiv and ebv represent interesting population targets to study the pathogenesis of hl, linking the evolution of the disease with viral infections. usually, patients ...201829316828
herpesviruses viral loads and levels of proinflammatory cytokines in apical periodontitis.this study aimed to analyse epstein-barr virus (ebv) and human cytomegalovirus (hcmv) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of tnf-α, il-1β, and il-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines .201829316040
levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by epstein-barr virus.to investigate whether apical periodontitis lesions infected by epstein-barr virus (ebv) exhibit higher levels of oxidative stress biomarkers (8-hydroxydeoxyguanosine (8-ohdg) and oxidized glutathione (gssg)) and bone resorption regulators (receptor activator of nuclear factor (nf-κb) ligand (rankl) and osteoprotegerin (opg)) compared to ebv negative periapical lesions and healthy pulp tissues.201829315650
tumor-specific t-cells engineered to overcome tumor immune evasion induce clinical responses in patients with relapsed hodgkin lymphoma.purpose transforming growth factor-β (tgf-β) production in the tumor microenvironment is a potent and ubiquitous tumor immune evasion mechanism that inhibits the expansion and function of tumor-directed responses; therefore, we conducted a clinical study to discover the effects of the forced expression of a dominant-negative tgf-β receptor type 2 (dnrii) on the safety, survival, and activity of infused tumor-directed t cells. materials and methods in a dose escalation study, eight patients with ...201829315015
quantitative pcr assays of cytomegalovirus and epstein-barr virus in hemophagocytic lymphohistiocytosis. 201829313310
novel x-linked inhibitor of apoptosis mutation in very early-onset inflammatory bowel disease child successfully treated with hla-haploidentical hemapoietic stem cells transplant after removal of αβ+ t and b cells.monogenic defects in genes related to primary immunodeficiencies can be responsible for inflammatory bowel disease (ibd). mutations in the x-linked inhibitor of apoptosis (xiap) gene have been described in several patients suffering from ibd and, in particular, with very early-onset inflammatory bowel disease (veoibd) features. we report a veoibd child with a novel xiap gene mutation characterized by a complicated disease course, which is unresponsive to several medical treatment options. a next ...201729312354
epstein-barr virus, but not cytomegalovirus, latency accelerates the decay of childhood measles and rubella vaccine responses-a 10-year follow-up of a swedish birth cohort.epstein-barr virus (ebv) and cytomegalovirus (cmv) are ubiquitous and persistent herpesviruses commonly acquired during childhood. both viruses have a significant impact on the immune system, especially through mediating the establishment of cellular immunity, which keeps these viruses under control for life. far less is known about how these viruses influence b-cell responses.201729312344
signaling by the epstein-barr virus lmp1 protein induces potent cytotoxic cd4+ and cd8+ t cell responses.the b-lymphotropic epstein-barr virus (ebv), pandemic in humans, is rapidly controlled on initial infection by t cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. if surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. the initial t cell response consists of predominantly cd8+ cytotoxic t cells and a smaller expansion of cd4+ cells. a major approach to treating ebv-associated lymphomas is adoptive transfer of autologous or allogenei ...201829311309
the aliens inside us: herv-w endogenous retroviruses and multiple sclerosis.two human endogenous retroviruses of the herv-w family are proposed as multiple sclerosis (ms) co-factors: ms-associated retrovirus (msrv) and ervwe1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. phase ii clinical trials against herv-wenv are ongoing. herv-w/msrv was repeatedly found in ms patients, in striking parallel with ms stages, active/remission phases, and therapy outcome. the herv-wenv protein is highly expressed in active ms pla ...201829307292
viruses in chronic progressive neurologic disease.viruses have long been implicated as triggers of disease onset and progression in multiple sclerosis (ms) and similar neuroinflammatory disorders. decades of epidemiological, molecular, and pathologic studies have most strongly linked the human herpesviruses epstein-barr virus (ebv) and human herpesvirus 6 (hhv-6) with ms. however, these viruses are ubiquitous in the general population and typically acquired decades before disease presentation, complicating the study of how they might contribute ...201829307291
new interactors of the truncated ebna-lp protein identified by mass spectrometry in p3hr1 burkitt's lymphoma cells.the epstein-barr virus nuclear antigen leader protein (ebna-lp) acts as a co-activator of ebna-2, a transcriptional activator essential for epstein-barr virus (ebv)-induced b-cell transformation. burkitt's lymphoma (bl) cells harboring a mutant ebv strain that lacks both the ebna-2 gene and 3' exons of ebna-lp express y1y2-truncated isoforms of ebna-lp (tebna-lp) and better resist apoptosis than if infected with the wild-type virus. in such bl cells, tebna-lp interacts with the protein phosphata ...201829303964
epstein-barr virus-positive large cell neuroendocrine carcinoma of the nasopharynx: report of a case with complete clinical and radiological response after combined chemoradiotherapy.neuroendocrine carcinomas of the head and neck are rare and are classified as well differentiated, moderately differentiated, and poorly differentiated carcinomas with the latter category being subdivided into small cell and large cell neuroendocrine carcinoma (lcnec). while most carcinomas in the nasopharynx are associated with epstein-barr virus (ebv), there has been only one previous report demonstrating a link between ebv and lcnec of the nasopharynx. in this report we describe a second case ...201829302900
identification of a novel, ebv-based antibody risk stratification signature for early detection of nasopharyngeal carcinoma in taiwan.epstein-barr virus (ebv) is necessary for the development of nasopharyngeal carcinoma (npc). by adulthood, ~90% of individuals test ebv-positive, but only a fraction develop cancer. factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective.201829301829
amegakaryocytic thrombocytopenia and subsequent aplastic anemia associated with apparent epstein-barr virus infection.acquired amegakaryocytic thrombocytopenia (aat), a rare entity characterized by severe thrombocytopenia and the absence of megakaryocytes in the bone marrow, may mimic or precede the diagnosis of aplastic anemia (aa). here, we describe a patient who presented with apparent epstein-barr virus (ebv)-associated immune thrombocytopenia resistant to several lines of therapies, which was in fact a form of aat with some features of aa. he eventually responded to therapy with eltrombopag, cyclosporine a ...201829301129
childhood nasopharyngeal carcinoma: state-of-the-art, and questions for the future.in children, nasopharyngeal carcinoma (npc) is a very rare tumor, mostly epstein-barr virus related and quite always diagnosed at a locally advanced stage. with current protocols associating induction cisplatin-based chemotherapy and concomitant chemoradiotherapy, prognosis is excellent with overall survival higher than 85%. however, long-term toxicities are frequent. improvement in radiation therapy modalities like intensity-modulated radiation therapy and new strategies with radiation dose ada ...201829300240
association of epstein - barr virus and breast cancer in eritrea.the oncogenic potential of epstein-barr virus (ebv) in breast cancer is being increasingly recognized. despite some controversies regarding such role, new evidence is suggesting a culpability of ebv in breast cancer, particularly in africa where the virus has been originally associated with causation of several solid and hematological malignancies. one example is a report from sudan implicating ebv as a prime etiologic agent for an aggressive type of breast cancer, where nearly 100% of tumor tis ...201729299053
the impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation.viral infections remain one of the most important complications following allogeneic hsct. few reports compare virus infection between different donor types in pediatric patients. we retrospectively analyzed viral infections and the outcome of one hundred and seventy-one pediatric patients (median 7.38 years) who underwent allogeneic hsct from matched related donor (mrd, n = 71), 10 of 10 hla allele-matched unrelated donors (mud1; n = 29), 9 of 10 hla allele-matched unrelated donors (mud2; n = 4 ...201829297965
concurrent diffuse large b-cell lymphoma and epstein-barr virus-associated smooth muscle tumour in the small bowel of an hiv-positive adult-a case report and review of the literature. 201829297137
the oncogenic membrane protein lmp1 sequesters traf3 in b-cell lymphoma cells to produce functional traf3 deficiency.loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (traf3) are commonly found in human b-cell malignancies, especially multiple myeloma and b-cell lymphoma (bcl). b-cell traf3 deficiency results in enhanced cell survival, elevated activation receptor signaling, and increased activity of certain transcriptional pathways regulating expression of prosurvival proteins. a recent analysis of traf3 protein staining of ∼300 human bcl tis ...201729296923
checkpoint blockade in hodgkin and non-hodgkin lymphoma.classical hodgkin lymphoma (chl) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of pd-1 ligands. this likely underlies the unique sensitivity of chl to pd-1 blockade, with response rates of ∼70% in relapsed/refractory disease. there are now numerous clinical trials testing pd-1 inhibitors in earlier stages of treatment and in combination with many other therapies. in general, non-hodgkin lymphomas (nhls) do not display a high frequency of ...201729296917
clinicopathologic consensus study of gray zone lymphoma with features intermediate between dlbcl and classical hl.gray zone lymphoma (gzl) is described as sharing features with classical hodgkin lymphoma (chl) and diffuse large b-cell lymphoma (dlbcl). however, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. sixty-eight cases diagnosed as gzl across 15 north american academic centers were evaluated by central pathology review to achieve consensus. of these, only 26 (38%) were confirmed as gzl. morphology was critical to gzl consensus diagnosis (eg, ...201729296913
long-term control of recurrent or refractory viral infections after allogeneic hsct with third-party virus-specific t cells.donor-derived adoptive t-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. off-the-shelf, third-party virus-specific t cells (vsts) appear promising, but the long-term safety and durability of responses have yet to be established. we conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (hsct) patients with persistent or recurrent cytomegalovirus (cmv) ...201729296867
high proportions of pd-1+ and pd-l1+ leukocytes in classical hodgkin lymphoma microenvironment are associated with inferior outcome.immune checkpoint inhibition targeting the programmed death receptor (pd)-1 pathway is a novel treatment approach in relapsed and refractory classical hodgkin lymphoma (chl). identifying patients with a high risk of treatment failure could support the use of pd-1 inhibitors as front-line treatment. our aim was to investigate the prognostic impact of pd-1, programmed death-ligand 1 (pd-l1), and pd-l2 in the tumor microenvironment in diagnostic biopsies of patients with chl. patients from denmark ...201729296784
th17 immune microenvironment in epstein-barr virus-negative hodgkin lymphoma: implications for immunotherapy.classical hodgkin lymphoma (chl) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive pd-1/pd-l1 pathway. although anti-pd-1 therapy can be effective in >60% of patients with refractory chl, improved treatment options are needed for chls which are resistant to anti-pd-1 or relapse after this form of immunotherapy. a deeper understanding of immunologic factors in the chl microenvironment might support the design of more effective treatm ...201729296775
alternative donor hematopoietic stem cell transplantation for sickle cell disease.most patients who could be cured of sickle cell disease (scd) with stem cell transplantation do not have a matched sibling donor. successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with scd. the use of a reduced-intensity conditioning regimen may decrease late adverse effects. ten patients with symptomatic scd underwent cd34+ cell-selected, t-cell-depleted peripheral blood stem cell transplantation from a mismatched family mem ...201729296761
epstein-barr virus dna in serum as an early prognostic marker in children and adolescents with hodgkin lymphoma.assay of cell-free dna in blood offers an approach to assessment of tumor dna. we sought to determine whether epstein-barr virus (ebv) dna in cell-free blood is also a good surrogate for the presence of tumor dna in children with hodgkin lymphoma, as it is in adults, and whether it correlates with pediatric outcomes. pediatric patients enrolled in a children's oncology group trial (ahod0031) were studied at baseline and at 8 days after the initiation of treatment. at baseline, ebv dna in cell-fr ...201729296710
micrornas sequencing unveils distinct molecular subgroups of plasmablastic lymphoma.plasmablastic lymphoma (pbl) is an aggressive lymphoma, often arising in the context of immunodeficiency and associated with epstein-barr virus (ebv) infection. the most frequently detected genetic alteration is the deregulation of myc gene through the translocation - t(8;14)(q24;q32). the diagnosis of pbl is often challenging because it has an overlap in morphology, immunophenotype, cytogenetics and virus association with other lymphomas and plasma cell neoplasms; further, its molecular basis r ...201729296171
chemokine ccl27 is a novel plasma biomarker for identification the nasopharyngeal carcinoma patients from the epstein-barr virus capsid antigen-specific iga seropositive population.to investigate the predictive value of chemokine ccl27 for identifying early stage nasopharyngeal carcinoma (npc) patients within a population seropositive for epstein-barr virus (ebv) capsid antigen-specific iga (vca-iga).201829295705
bacterial artificial chromosomes establish replication timing and sub-nuclear compartment de novo as extra-chromosomal vectors.the role of dna sequence in determining replication timing (rt) and chromatin higher order organization remains elusive. to address this question, we have developed an extra-chromosomal replication system (e-bacs) consisting of ∼200 kb human bacterial artificial chromosomes (bacs) modified with epstein-barr virus (ebv) stable segregation elements. e-bacs were stably maintained as autonomous mini-chromosomes in ebna1-expressing hela or human induced pluripotent stem cells (hipscs) and established ...201729294101
azathioprine-induced reversible ebv-associated hodgkin-like lymphoma after immunosuppressive therapy for autoimmune hepatitis
.the use of immunosuppressive agents is associated with an increased risk of the development of certain types of malignancies, particularly lymphoma. many of these lymphomas are associated with epstein-barr virus (ebv), which might be reactivated under immunosuppression. we present the case of a patient with an autoimmune hepatitis who developed ebv-associated hodgkin-like lymphoma under immunosuppressive treatment with azathioprine. the tumor regressed spontaneously after withdrawal of azathiopr ...201829292695
ephrin receptor a2 is a functional entry receptor for epstein-barr virus.epstein-barr virus (ebv) is an oncogenic virus that infects more than 90% of the world's population 1 . ebv predominantly infects human b cells and epithelial cells, which is initiated by fusion of the viral envelope with a host cellular membrane 2 . the mechanism of ebv entry into b cells has been well characterized 3 . however, the mechanism for epithelial cell entry remains elusive. here, we show that the integrins αvβ5, αvβ6 and αvβ8 do not function as entry and fusion receptors for epitheli ...201829292384
ephrin receptor a2 is an epithelial cell receptor for epstein-barr virus entry.epstein-barr virus (ebv) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various b cell lymphomas 1 . ebv infects both b cells and epithelial cells 2 . recently, we reported that epidermal growth factor and neuropilin 1 markedly enhanced ebv entry into nasopharyngeal epithelial cells 3 . however, knowledge of how ebv infects epithelial cells remains incomplete. to understand the mechanisms through which ebv infects epithelial cells, we integrated microarray and ...201829292383
open splenectomy for varicella zoster induced spontaneous splenic rupture.here we present a case of atraumatic splenic rupture secondary to varicella infection requiring emergency splenectomy. the presentation was as would be expected for epstein barr virus (ebv) related splenic injury, which is well documented in the literature. dermatological findings however suggested varicella zoster, and viral serology subsequently confirmed the diagnosis.201729291540
lymphoepithelioma-like carcinoma of the large intestine: a case report and literature review.lymphoepithelioma like carcinoma (lelc) is a well-known neoplastic lesion that mainly involves the stomach and which has been linked to epstein barr virus infection. there are exceptional cases of intestinal involvement by lelc, with 7 reported cases to date. we report a new case of lelc affecting the right colon and review the literature on this rare disorder, with special emphasis on pathogenesis, molecular features and differential diagnosis.201829290316
myastenia and small doses of ionizing radiation: experience of successful use of rituximab for treatment of an irradiated with myasthenia gravis.a clinical case of the rituximab («rituksim», «mabthera») use to treat a man affected by the chornobyl npp acci dent with malignant resistant form of myasthenia gravis in conjunction with chronic mixed infection by toxoplasma, epstein barr virus, cytomegalovirus and herpes simplex virus is described. in the dynamics of two year's observa tion the clinical efficacy of monoclonal antibodies was shown as the main symptoms stabilization and reducing doses of glucocorticoid and anticholinergic therap ...201729286523
impact of chronic blood viral infection on lymphocyte telomere length in chornobyl clean-up workers in a remote period after radiation exposure.to assess whether telomere length in lymphocytes of chornobyl clean up workers at a late period 30 years after the exposure to ionizing radiation is influenced by a chronic blood viral infection and to determine role of viral carriage in cellular senescence.201729286521
low uric acid level increases the risk of infectious mononucleosis and this effect is more pronounced in women.infectious mononucleosis (im) due to epstein-barr virus infection is common. uric acid (ua) is an important endogenous antioxidant. to the best of our knowledge, the association between ua and im has not been comprehensively investigated to date. the aim of the present study was to investigate this association in chinese patients. a total of 95 patients (47 men and 48 women) with im were recruited, along with 95 healthy controls. clinical data were classified by patient sex. receiver operating c ...201729285370
elevated pretreatment platelet distribution width and platelet count predict poor prognosis in nasopharyngeal carcinoma.previous studies have demonstrated that platelets play a multifaceted role in cancer progression and metastasis. however, the value of platelet indices for predicting survival in nasopharyngeal carcinoma (npc) patients remains unknown. the aim of this study was to evaluate the predictive significance of platelet indices in npc cases.201729285316
cadherin 6 is activated by epstein-barr virus lmp1 to mediate emt and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.nasopharyngeal carcinoma (npc) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. epstein-barr virus (ebv) infection plays a fundamental role in npc development with the mechanism is not well understood. here we demonstrate that ebv oncoprotein lmp1 drives emt and metastasis of npc by reactivating the adhesion molecule, cadherin 6 (cdh6), which normally occurs in embryogenesis with unknown role in npc. cdh6 was found to be upregulated in lmp1 ...201729284791
prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum epstein-barr virus dna copy number in predicting distant metastasis in patients with n1 nasopharyngeal carcinoma.according to the 7th edition of the american joint committee on cancer (ajcc) staging system, over 50% of patients with nasopharyngeal carcinoma (npc) have n1 disease at initial diagnosis. however, patients with n1 npc are relatively under-researched, and the metastasis risk of this group is not well-stratified. this study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (gtvnd) and pretreatment serum copy number of epstein-barr virus (ebv) dna in p ...201729284539
loss of rasgrp1 in humans impairs t-cell expansion leading to epstein-barr virus susceptibility.inherited ctps1, cd27, and cd70 deficiencies in humans have revealed key factors of t-lymphocyte expansion, a critical prerequisite for an efficient immunity to epstein-barr virus (ebv) infection. rasgrp1 is a t-lymphocyte-specific nucleotide exchange factor known to activate the pathway of map kinases (mapk). a deleterious homozygous mutation in rasgrp1 leading to the loss rasgrp1 expression was identified in two siblings who both developed a persistent ebv infection leading to hodgkin lymphoma ...201729282224
a rare case of classical hodgkin lymphoma diagnosed 10 years after liver transplant.posttransplant lymphoproliferative disorders (ptld) represent a rare and potentially life-threatening complication after liver transplantation. classical hodgkin lymphoma (chl), with an incidence of approximately 1.8-3.4% of all ptld cases, represents a minority of ptld, mainly presenting as a late transplant complication. the main risk factors for the development of ptld are epstein-barr virus (ebv) infection and intensive immunosuppression. however, other risk factors like hepatitis c virus ma ...201729279693
other iatrogenic immunodeficiency-associated lymphoproliferative disorder, hodgkin type, following epstein-barr viral hepatitis in a patient with rheumatoid arthritis.a 59-year-old man with an 18-year history of rheumatoid arthritis who had been treated with steroids, methotrexate, and infliximab presented with a high-grade fever, cervical lymphadenopathy, and hepatosplenomegaly. epstein-barr virus (ebv) hepatitis was diagnosed based on the liver histology and ebv antibody titer. the symptoms improved temporarily, but five months later, the fever, skin rash, jaundice, and thrombocytopenia relapsed. bone marrow and liver biopsies demonstrated infiltration with ...201729279493
lymphoblastoids cell lines - derived ipsc line from a 26-year-old myotonic dystrophy type 1 patient carrying (ctg)200 expansion in the dmpk gene: chuqi001-a.human immortalized epstein-barr virus (ebv) lymphoblastoids cells line (lcls) from a 26-year- old male affected by an adult form of myotonic dystrophy type 1 (dm1) disease and carrying 200 ctg repeats mutation in the blood was used to generate induced pluripotent stem cells (ipscs) using the sendai virus expressing klf4, oct4, sox2 and c-myc. the resulting ipscs were ebv free, expressed the pluripotency markers, could be differentiated into the three germ layers in vitro, had a normal karyotype, ...201729274549
epstein-barr virus exanthem in an adult patient with myelodysplastic syndrome. 201729274098
inverse correlation of vδ2+ t-cell recovery with ebv reactivation after haematopoietic stem cell transplantation.epstein-barr virus (ebv) reactivation remains a life-threatening complication in recipients of a haploidentical haematopoietic stem cell transplantation (haplohsct). reconstitution of adaptive t lymphocytes is generally compromised at the early stages following transplant, suggesting an important role of other effector cells in preventing ebv infection. our previous studies demonstrated that recovery of cd4- cd8- t cells negatively correlated with ebv reactivation after haplohsct. in this prospe ...201829270985
disseminated tuberculosis and chronic mucocutaneous candidiasis in a patient with a gain-of-function mutation in signal transduction and activator of transcription 1.in humans, recessive loss-of-function mutations in stat1 are associated with mycobacterial and viral infections, whereas gain-of-function (gof) mutations in stat1 are associated with a type of primary immunodeficiency related mainly, but not exclusively, to chronic mucocutaneous candidiasis (cmc). we studied and established a molecular diagnosis in a pediatric patient with mycobacterial infections, associated with cmc. the patient, daughter of a non-consanguineous mestizo mexican family, had axi ...201729270166
mirna-36 inhibits kshv, ebv, hsv-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (ifitm1).kaposi's sarcoma-associated herpesvirus (kshv) is etiologically associated with all forms of kaposi's sarcoma worldwide. little is currently known about the role of micrornas (mirnas) in kshv entry. we recently demonstrated that kshv induces a plethora of host cell mirnas during the early stages of infection. in this study, we show the ability of host cell novel mir-36 to specifically inhibit kshv-induced expression of interferon induced transmembrane protein 1 (ifitm1) to limit virus infection ...201729269892
functional assessment of the bmpr2 gene in lymphoblastoid cell lines from graves' disease patients.in this study, we analysed the possible influence of the c.419-43delt bmpr2 variant in patients with graves' disease (gd), in a molecular basis, focusing our efforts on possible alterations in the mrna processing and synthesis. the molecular assessment of this variant in patients with gd would shed light on the association between the bmpr2 gene and the disease. the variant was detected in 18%, 55% and 10% of patients with pulmonary arterial hypertension, gd and in general population, respective ...201729266775
the optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients receiving additional induction chemotherapy.to clarify the optimal cumulative cisplatin dose (ccd) in locoregionally-advanced nasopharyngel carcinoma (npc) patients receiving induction chemotherapy (ic) plus concurrent chemoradiotherapy (ccrt). using the npc-specific database from the established big-data intelligence platform at sun yat-sen university cancer center, 583 non-disseminated, locoregionally-advanced npc patients receiving ic plus ccrt were enrolled. propensity score matching (psm) analysis was conducted to control for confoun ...201729266526
rediscovery of nf-κb signaling in nasopharyngeal caicrnoma: how genetic defects of nf-κb pathway interplay with ebv in driving oncogenesis?nasopharyngeal carcinoma (npc) is a unique ebv-associated subtype of head and neck cancer, which has the highest incidence in southern china and eastern south asia. the interaction between genetic risk factors and environmental challenge, have been considered to contribute to the development of nasopharyngeal carcinogenesis. constitutive activation of nf-κb signaling has been seen in npc tissues and is associated with unfavorable prognosis. recently, several whole exome sequencing study consiste ...201729266238
serological evidence of borrelia burgdorferi infection in mexican patients with facial palsy.facial palsy is the most frequent manifestation of neuroborreliosis in the united states, europe, and asia, whereas in mexico, its frequency is unknown.201729265112
aggressive natural killer cell leukemia: a case report.aggressive natural killer (nk) cell leukemia is a rare hematological malignancy. it often presents with a rapidly declining clinical course and a poor prognosis with a median survival of a few months. we report the case of a 23-year-old man with high fever, enlarged lymph nodes, splenomegaly, cytopenia, liver dysfunctions, coagulation disorders and hemophagocytosis. computed tomography scan showed right lung shadow. lung involvement was considered. histological examination of the lung was not pe ...201729263706
efficient translation of ebv dna polymerase contributes to the enhanced lytic replication phenotype of m81 ebv.epstein-barr virus (ebv) is linked to development of both lymphoid and epithelial malignancies worldwide. the m81 strain of ebv isolated from a chinese patient with nasopharyngeal carcinoma (npc) demonstrates spontaneous lytic replication and high-titer virus production in comparison to the prototype b95-8 ebv strain. genetic comparisons have previously been performed between m81 and b95-8 ebv in order to determine if the hyper-lytic property of m81 is associated with sequence differences in ess ...201729263273
[value of cd3+cd4+ t cell count in prediction of viral infection after hematopoietic stem cell transplantation in patients severe aplastic anemia].to explore the value of cd3+cd4+ t cell count in prediction of viral infections after allogeneic hematopoietic stem cell transplantation(allo-hsct) in the patients with severe aplastic anemia(saa).201729262912
[lymphocytic clonal expansion in adult patients with epstein-barr virus-associated lymphoproliferative disease].to explore the lymphocytic clonal expansion in adult patients with epstein-barr virus-associated lymphoproliferative diseases (ebv+lpd), and to investigate the experimental methods for ebv+lpd cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease.201729262893
b cell receptor activation and chemical induction trigger caspase-mediated cleavage of pias1 to facilitate epstein-barr virus reactivation.epstein-barr virus (ebv) in tumor cells is predominately in the latent phase, but the virus can undergo lytic reactivation in response to various stimuli. however, the cellular factors that control latency and lytic replication are poorly defined. in this study, we demonstrated that a cellular factor, pias1, restricts ebv lytic replication. pias1 depletion significantly facilitated ebv reactivation, while pias1 reconstitution had the opposite effect. remarkably, we found that various lytic trigg ...201729262325
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