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immune escape of γ-herpesviruses from adaptive immunity.epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) are two γ-herpesviruses identified in humans and are strongly associated with the development of malignancies. murine γ-herpesvirus (mhv-68) is a naturally occurring rodent pathogen, representing a unique experimental model for dissecting γ-herpesvirus infection and the immune response. these γ-herpesviruses actively antagonize the innate and adaptive antiviral responses, thereby efficiently establishing latent or persis ...201424733560
the epstein barr-encoded bart-6-3p microrna affects regulation of cell growth and immuno response in burkitt lymphoma.burkitt lymphoma is an aggressive b-cell lymphoma presenting in three clinical forms: endemic, sporadic and immunodeficiency-associated. more than 90% of endemic burkitt lymphoma carry latent epstein-barr virus, whereas only 20% of sporadic burkitt lymphoma are associated with epstein-barr infection. although the epstein-barr virus is highly related with the endemic form, how and whether the virus participates in its pathogenesis remains to be fully elucidated. in particular, the virus may impai ...201424731550
epitope distribution in ordered and disordered protein regions. part b - ordered regions and disordered binding sites are targets of t- and b-cell immunity.intrinsically disordered proteins exist in highly flexible conformational states linked to different protein functions. in this work, we have presented evidence that hla class-i- and class-ii-binding t-cell epitopes, experimentally verified in several tumor-associated antigens and nuclear systemic autoantigens, are predominantly located in ordered protein regions or at disorder/order borderlines, defined by the majority of analyzed publicly available disorder predictors. we have also observed th ...201424726865
il-27r-mediated regulation of il-17 controls the development of respiratory syncytial virus-associated pathogenesis.il-27 is a heterodimeric cytokine composed of the subunits p28 and epstein-barr virus induced gene (ebi)-3 and is known for its effects on t-cell function and differentiation. il-27 signals through the widely expressed il-27 receptor (il-27r), composed of the ligand-specific il-27rα chain and gp130. engagement of the il-27r activates stat1 signaling, induces the expression of the type 1 helper t-cell (th1) cytokine, interferon γ, and suppresses the differentiation of th2 and th17 cells. this stu ...201424726498
hypothesis: a role for ebv-induced molecular mimicry in parkinson's disease.current concepts regarding the pathogenesis of parkinson's disease support a model whereby environmental factors conspire with a permissive genetic background to initiate the disease. the identity of the responsible environmental trigger has remained elusive. there is incontrovertible evidence that aggregation of the neuronal protein alpha-synuclein is central to disease pathogenesis. a novel hypothesis of parkinson's pathogenesis, articulated by braak and colleagues, implicates a pathogen actin ...201424726430
metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma epstein-barr virus deoxyribonucleic acid.to investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (npc) patients with persistently detectable plasma epstein-barr virus dna (pebv dna) after curative radiation therapy plus induction/concurrent chemotherapy.201424725686
[extranodal nk/t-cell lymphoma].the prognosis of extranodal nk/t-cell lymphoma (enkl) used to be poor and this lymphoma was one of the most difficult lymphoma subtypes to treat. however, in recent years, novel treatment strategies have been applied, and the prognosis has greatly improved. simultaneous chemoradiotherapy is currently regarded as the standard for nasal enkl limited at most to neck lymph nodes. for advanced or relapsed enkl. l-asparaginase containing regimen such as smile or aspametdex is recommended. hematopoieti ...201424724414
[pathological diagnosis of mature t/nk cell lymphoma].peripheral t-cell lymphoma (ptcl) and natural killer/t-cell lymphoma (nktcl) are rare and heterogeneous forms of non-hodgkin lymphoma (nhl) that, in general, are associated with a poor clinical outcome. in addition, many subtypes are present in the world health organization (who) classification of ptcl. to well classify and diagnose the ptcl, clinical, molecular, morphological and phenotypic data are necessary. for example, human t-cell leukemia virus type 1 (htlv-i) provirus is necessary for th ...201424724401
hodgkin lymphoma incidence in california hispanics: influence of nativity and tumor epstein-barr virus.for classical hodgkin lymphoma (hl), migrant studies could elucidate contributions of environmental factors (including epstein-barr virus (ebv)) to the lower rates in non-whites. given the well-described etiologic complexity of hl, this research requires a large, immigrant population, such as california hispanics.201424722952
quantitative detection of epstein-barr virus dna in cerebrospinal fluid and blood samples of patients with relapsing-remitting multiple sclerosis.the presence of epstein-barr virus (ebv) dna in cerebrospinal fluid (csf) and peripheral blood (pb) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting ms (rrms) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative ebv dna detection. both cell-free and cell-associated csf and pb fractions were analyzed, to distinguish latent from lytic ebv infect ...201424722060
effects of a biologic agent in a patient with rheumatoid arthritis after treatment for methotrexate-associated b-cell lymphoma: a case report.several studies have suggested an increased risk of malignant tumor in patients with rheumatoid arthritis. it has been also reported that rheumatoid arthritis patients have a high incidence of lymphoma compared with the general population, and that patients receiving methotrexate, which is the anchor drug for rheumatoid arthritis treatment, can develop lymphoproliferative disease. nevertheless, management of rheumatoid arthritis after treatment for methotrexate-associated lymphoma has not been f ...201424721419
the effect of astragalus polysaccharide on the epstein-barr virus lytic cycle.effects of a polysacharide from chinese herbal plant astragalus membranaceus (aps) on the expression of epstein-barr virus (ebv) immediate early proteins zta, rta and ea-d in raji cells were examined. ebv switch from latent to lytic cycle in raji cells was induced by 12-o-tetradecanoylphorbol-13-acetate (tpa) and sorbol butyrate (sb) and the effects of aps were examined by immunofluorescence, western blotting and flow cytometry. aps in a non-cytotoxic concentration of 30 μg/ml significantly supp ...201424717032
diagnostic significance of combined detection of epstein-barr virus antibodies, vca/iga, ea/iga, rta/igg and ebna1/iga for nasopharyngeal carcinoma.the objective of this study was to investigate the diagnostic significance of ebv antibody combined detection for nasopharyngeal carcinoma (npc) in a high incidence region of southern china. two hundred and eleven untreated npc patients, 203 non-npc ent patients, and 210 healthy controls were recruited for the study. the titers of vca/iga and ea/iga were assessed by immunoenzyme assay, and the levels of rta/igg and ebna1/iga were determined by enzyme-linked immunosorbent assay. the levels of vca ...201424716925
first-in-man clinical results with good manufacturing practice (gmp)-compliant polypeptide-expanded adenovirus-specific t cells after haploidentical hematopoietic stem cell transplantation.adoptive immunotherapy against viral infections is a promising treatment option for patients after hematopoietic stem cell transplantation. however, the generation of virus-specific t cells is either cost-intensive or time-consuming. we developed the first gmp-compliant protocol to generate donor-derived adenovirus (hadv), cytomegalovirus, and epstein-barr virus-specific t-cell lines (tcls) within 12 days by the use of overlapping polypeptides derived from different viruses in combination with i ...201424714358
4-1bb-based isolation and expansion of cd8+ t cells specific for self-tumor and non-self-tumor antigens for adoptive t-cell therapy.adoptive t-cell therapy is a promising approach to the immunotherapy of cancer, but for it to be a general cancer therapy a simple and standardized procedure for producing tumor-specific cd8 t cells is needed. on the basis of a unique property of 4-1bb (cd137), the selective expression on activated t cells, we have developed a simple and practical protocol to produce antigen-specific cd8 t cells from peripheral blood mononuclear cells. we have proved the feasibility of this procedure by isolatin ...201424714356
complementation of antigen-presenting cells to generate t lymphocytes with broad target specificity.antigen-specific t cells provide a therapy for cancer that is highly specific, self-replicating, and potentially devoid of toxicity. ideally, tumor-specific t cells should recognize multiple epitopes on multiple antigens to prevent tumor immune escape. however the large-scale expansion of such broad-spectrum t cells has been limited by the availability of potent autologous antigen-presenting cells that can present antigens on the polymorphic array of each patient's hla allotype. we evaluated a n ...201424714353
mitotic stability of small supernumerary marker chromosomes: a study based on 93 immortalized cell lines.small supernumerary marker chromosomes (ssmc) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. however, no detailed studies have been done for the mitotic stability of ssmc so far, mainly due to the lack of a corresponding in vitro model system. recently, we established an ssmc-cell bank (else kröner-fresenius-ssmc-cellbank) with >150 cell lines. therefore, 93 selected ssmc cases were studied here for the presence of the correspon ...201424714101
fatal missed case of hemophagocytic lymphohistiocytosis co-infected with parvovirus b19 and epstein-barr virus in an infant: test hyperferritinaemia early.hemophagocytic lymphohistiocytosis (hlh) triggered by parvovirus b19 and epstein-barr virus co-infection is rare and unknown in infants. a 2-month-old male infant with fever, rash, bicytopenia and hepato-splenomegaly died owing to diagnostic dilemmas. hence simply testing for hyperferritinaemia and hypertriglyceridemia/hypofibrinogenemia could diagnose hlh early while robust treatment be life-saving.201424713910
anti-tumor effects of suberoylanilide hydroxamic acid on epstein-barr virus-associated t cell and natural killer cell lymphoma.the ubiquitous epstein-barr virus (ebv) infects not only b cells but also t cells and natural killer (nk) cells and is associated with various lymphoid malignancies. recent studies have reported that histone deacetylase (hdac) inhibitors exert anticancer effects against various tumor cells. in the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (saha), an hdac inhibitor, on ebv-positive and ebv-negative t and nk lymphoma cells. several eb ...201424712440
dysfunction of mitochondria due to environmental carcinogens in nasopharyngeal carcinoma in the ethnic group of northeast indian population.nasopharyngeal carcinoma (npc) is a rare cancer worldwide, but in india, npc is uncommon in its subcontinent except in the north-eastern part of the country. npc is thought to be caused by the combined effects of environmental carcinogens, genetic susceptibility and epstein-barr virus (ebv). this is the first study that aimed to examine the selected risk factors, mostly dietary, viral environmental, metabolic gene polymorphisms, mitochondrial dna (mtdna) copy number variation and their risk, in ...201424711137
epstein-barr virus serology as a potential screening marker for nasopharyngeal carcinoma among high-risk individuals from multiplex families in taiwan.nasopharyngeal carcinoma (npc) is an epstein-barr virus (ebv)-associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. however, npc is typically diagnosed at advanced stages, in which disease-free survival is <50%. there is, therefore, a need for clinical tools to assist in early npc detection, particularly among high-risk individuals.201424769890
arid1a/baf250a as a prognostic marker for gastric carcinoma: a study of 2 cohorts.arid1a/baf250a has been recently implicated as a tumor suppressor in gastric cancer. we sought to clarify the clinical significance of baf250a/arid1a in relation to other clinical parameters and relevant biomarkers in gastric carcinoma. cases from 2 separate cohorts of patients with gastric carcinoma from vancouver (n = 173) and toronto (n = 80) were selected for the construction of tissue microarrays, which were used to assess the immunohistochemical status of baf250a (anti-arid1a), mismatch re ...201424767857
primary undifferentiated carcinoma of the trachea.primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. tracheal localization is exceedingly rare. to the best of our knowledge, only four cases have been reported previously, all in asian patients.201424765831
primary burkitt's lymphoma of the thyroid without epstein-barr virus infection: a case report and literature review.primary thyroid lymphomas are rare, and the majority are b-cell lymphoma. primary burkitt's lymphoma (bl) of the thyroid is much less common than the other types of lymphoma. the current study presents the case of an eight-year-old male with a mass in the right lobe of the thyroid, which was detected by b-ultrasound. the patient was diagnosed with bl by immunohistochemistry, fluorescence in situ hybridization analysis of myc (8q24) and immunoglobulin rearrangement assays. furthermore, subsequent ...201424765169
cd30(+) extranodal natural killer/t-cell lymphoma mimicking phlegmonous myositis: a case report.the current study presents a case of a 23-year-old male with cd30(+) nasal-type extranodal natural killer/t-cell lymphoma (nktl), with unusual clinical features mimicking phlegmonous myositis. the patient initially presented with swelling and tenderness of the left lower limb, particularly around the left ankle. one month later, pharyngalgia and fever developed and the patient was treated with antibiotics for the phlegmonous inflammation, however, the symptoms were not relieved. a muscle biopsy ...201424765148
discerning primary tumors from metastases in synchronous nasopharyngeal squamous cell carcinoma and cutaneous squamous cell carcinoma: a case report and review of the literature.nasopharyngeal carcinoma is one of the most common types of malignant tumor in southern china and southeast asia, and its etiology is closely associated with epstein-barr virus (ebv) infection. non-keratinizing carcinoma accounts for >95% of all nasopharyngeal carcinoma cases. in addition, metastatic nasopharyngeal carcinoma from other locations in the body is extremely rare. this study reports the case of a 53-year-old female who presented with a lesion on the left nasal alar skin that had slow ...201424765143
human b cell-derived lymphoblastoid cell lines constitutively produce fas ligand and secrete mhcii(+)fasl(+) killer exosomes.immune suppression mediated by exosomes is an emerging concept with potentially immense utility for immunotherapy in a variety of inflammatory contexts, including allogeneic transplantation. exosomes containing the apoptosis-inducing molecule fas ligand (fasl) have demonstrated efficacy in inhibiting antigen-specific immune responses upon adoptive transfer in animal models. we report here that a very high frequency of human b cell-derived lymphoblastoid cell lines (lcl) constitutively produce mh ...201424765093
epstein-barr virus-negative post-transplant lymphoproliferative diseases: three distinct cases from a single center.three cases of epstein-barr virus (ebv)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. the patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large b-cell lymphoma, and atypical burkitt lymphoma. absence of ebv in the tissue samples was demonstrated by both in situ hybridization for ebv early rna and polymerase chain reaction for ebv dna. patients were treated with reduction in i ...201424764734
viruses as potential pathogenic agents in systemic lupus erythematosus.genetic and environmental factors appear to contribute to the pathogenesis of systemic lupus erythematosus (sle). viral infections have been reported to be associated with the disease. a number of exogenous viruses have been linked to the pathogenesis of sle, of which epstein-barr virus (ebv) has the most evidence of an aetiological candidate. in addition, human endogenous retroviruses (herv), hres-1, erv-3, herv-e 4-1, herv-k10 and herv-k18 have also been implicated in sle. hervs are incorporat ...201424763543
in vivo intratumoral epstein-barr virus replication is associated with xbp1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications.post-transplant lymphoproliferative disorders are life-threatening complications following hematopoietic or solid organ transplantation. they represent a spectrum of mostly ebv-driven lymphoplasmacytic proliferations. while the oncogenic effect of ebv is related to latent infection, lytic infection also has a role in lymphomagenesis. in vitro, ebv replication is linked to plasma cell differentiation and xbp1 activation, although this phenomenon has never been addressed in vivo. we analyzed for t ...201424762547
epstein-barr virus–associated lymphocytosis masquerading as lymphoma. 201424761435
contribution of il-12/il-35 common subunit p35 to maintaining the testicular immune privilege.the testis is an organ with immune privilege. the comprehensive blood-testis barrier formed by sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body's immune system. the interleukin (il)-6/il-12 family cytokines il-12 (p35/p40), il-23 (p19/p40), il-27 (p28/epstein-barr virus-induced gene 3 [ebi3]), and il-35 (p35/ebi3) play critical roles in the regulation of various immune responses, but their roles in testicular immune privilege are not well understood. in t ...201424760014
identification of protein kinase inhibitors with a selective negative effect on the viability of epstein-barr virus infected b cell lines.epstein-barr virus (ebv) is a human herpesvirus, which is causally associated with the development of several b lymphocytic malignancies that include burkitt's lymphomas, hodgkin's disease, aids and posttransplant associated lymphomas. the transforming activity of ebv is orchestrated by several latent viral proteins that mimic and modulate cellular growth promoting and antiapoptotic signaling pathways, which involve among others the activity of protein kinases. in an effort to identify small mol ...201424759913
synchronous hiv/aids-related epstein-barr virus-associated smooth muscle tumors in a 20-year-old female.we present a case of simultaneous endobronchial and adrenal epstein-barr virus-associated smooth muscle tumors in a 20-year-old female with aids. blood epstein-barr virus polymerase chain reaction was negative at the time of diagnosis.201424759574
a molecular basis for the interplay between t cells, viral mutants, and human leukocyte antigen micropolymorphism.mutations within t cell epitopes represent a common mechanism of viral escape from the host protective immune response. the diverse t cell repertoire and the extensive human leukocyte antigen (hla) polymorphism across populations is the evolutionary response to viral mutation. however, the molecular basis underpinning the interplay between hla polymorphism, the t cell repertoire, and viral escape is unclear. here we investigate the t cell response to a hla-b*35:01- and hla-b*35:08-restricted (40 ...201424759101
epstein-barr virus-positive diffuse large b-cell lymphoma in an elderly patient.epstein-barr virus-positive (ebv) diffuse large b-cell lymphoma (dlcbl) of the elderly is a newly described lymphoproliferative disorder that arises in elderly patients without a predisposing immunodeficiency. clinical features at presentation may include lymphadenopathy, b-symptoms and extranodal involvement. the main sites of extranodal involvement are the skin, lung, tonsil and stomach. histopathological findings include atypical large lymphoid cells with variable amounts of reactive cells, s ...201424758493
epimir: a database of curated mutual regulation between mirnas and epigenetic modifications.as two kinds of important gene expression regulators, both epigenetic modification and microrna (mirna) can play significant roles in a wide range of human diseases. recently, many studies have demonstrated that epigenetics and mirna can affect each other in various ways. in this study, we established the epimir database, which collects 1974 regulations between 19 kinds of epigenetic modifications (such as dna methylation, histone acetylation, h3k4me3, h3s10p) and 617 mirnas across seven species ...201424682734
genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1,000 genomes project.most people in the world (∼90%) are infected by the epstein-barr virus (ebv), which establishes itself permanently in b cells. infection by ebv is related to a number of diseases including infectious mononucleosis, multiple sclerosis, and different types of cancer. so far, only seven complete ebv strains have been described, all of them coming from donors presenting ebv-related diseases. to perform a detailed comparative genomic analysis of ebv including, for the first time, ebv strains derived ...201424682154
identification and characterization of small molecule modulators of the epstein-barr virus-induced gene 2 (ebi2) receptor.oxysterols have recently been identified as natural ligands for a g protein-coupled receptor called ebi2 (aka gpr183) ( nature 2011 , 475 , 524 ; 519 ). ebi2 is highly expressed in immune cells ( j. biol. chem. 2006 , 281 , 13199 ), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type i diabetes ( nature 2010 , 467 , 460 ). here we describe the isolation of a potent small molecule antagonist for the ...201424678947
ebv seroepidemiology in married and unmarried women and men in iran.among the eight known human herpes viruses, epstein- barr virus (ebv) is considered to be sexually transmissible. this study was conducted to evaluate the seroepidemiology of this infection in married and unmarried iranian couples.201426989728
lymphomatoid granulomatosis of central nervous system and lung driven by epstein barr virus proliferation: successful treatment with rituximab-containing chemotherapy.lymphomatoid granulomatosis (lyg) is a very rare epstein-barr virus (ebv) associated b-cell lymphoproliferative disorder. we report the case of a 41-year-old man who presented with fever and respiratory symptoms. computed tomography showed multiple nodules in both lung fields. polymerase chain reaction (pcr) analysis for ebv was positive in bronchoalveolar lavage and biopsy of lung node yielded a diagnosis of lyg, grade iii. shortly after initiation of treatment with agressive chemotherapy, neur ...201424678394
structural and functional characterization of a complex between the acidic transactivation domain of ebna2 and the tfb1/p62 subunit of tfiih.infection with the epstein-barr virus (ebv) can lead to a number of human diseases including hodgkin's and burkitt's lymphomas. the development of these ebv-linked diseases is associated with the presence of nine viral latent proteins, including the nuclear antigen 2 (ebna2). the ebna2 protein plays a crucial role in ebv infection through its ability to activate transcription of both host and viral genes. as part of this function, ebna2 associates with several host transcriptional regulatory pro ...201424675874
the rad6/18 ubiquitin complex interacts with the epstein-barr virus deubiquitinating enzyme, bplf1, and contributes to virus infectivity.epstein-barr virus (ebv) encodes bplf1, a lytic cycle protein with deubiquitinating activity that is contained in its n-terminal domain and conserved across the herpesviridae. ebv replication is associated with cellular dna replication and repair factors, and initiation of ebv lytic replication induces a dna damage response, which can be regulated at least in part by bplf1. the cellular dna repair pathway, translesion synthesis (tls), is disrupted by bplf1, which deubiquitinates the dna processi ...201424672041
module function and two-way clustering analysis of epstein-barr virus-related nasopharyngeal cancer.this study sought to identify and characterize the function of genes as diagnostic markers for epstein-barr virus (ebv)-related nasopharyngeal cancer (npc). the gene expression profile of gse13597 was downloaded from the gene expression omnibus database, which included 28 ebv-related npc gene expression profile data sets, 25 disease samples, and 3 control samples. data were pre-processed, and differentially expressed genes were screened using the r language. the co-expression coefficient was cal ...201424668670
clinicopathological and ebv analysis of respiratory epithelial adenomatoid hamartoma.to investigate the clinicopathological characteristics of respiratory epithelial adenomatoid hamartoma (reah) in residents of southern china and to study the correlation between reah and epstein-barr virus (ebv).201424667091
adapted treatment of epstein-barr virus infection to prevent posttransplant lymphoproliferative disorder after heart transplantation.up to 35% of posttransplant lymphoproliferative disorder (ptld) cases occur within 1 year of transplantation, and over 50% are associated with epstein-barr virus (ebv). ebv primary infection and reactivation are ptld predictive factors, but there is no consensus for their treatment. we conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive ebv viral-load measurements and endomyocardial b ...201424666832
age-associated epstein-barr virus-specific t cell responses in seropositive healthy adults.epstein-barr virus (ebv) is present in 95% of the world's adult population. the immune response participates in immune vigilance and persistent infection control, and this condition is maintained by both a good quality (functionality) and quantity of specific t cells throughout life. in the present study, we evaluated ebv-specific cd4(+) and cd8(+) t lymphocyte responses in seropositive healthy individuals younger and older than 50 years of age. the assessment comprised the frequency, phenotype, ...201424666437
epstein-barr virus bzlf1 gene polymorphisms: malignancy related or geographically distributed variants?the ubiquitous epstein-barr virus (ebv) is related to the development of several lymphoid and epithelial malignancies and is also the aetiological agent for infectious mononucleosis (im). bzlf1, an immediate early gene, plays a key role in modulating the switch from latency to lytic replication, hence enabling viral propagation. polymorphic variations in the coded protein have been studied in other geographical regions in a search for viral factors that are inherent to malignancies and differ fr ...201424666405
targeting epstein-barr virus oncoprotein lmp1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy.our goal in this work was to illustrate the epstein-barr virus (ebv)-modulated global biochemical profile and provide a novel metabolism-related target to improve the therapeutic regimen of nasopharyngeal carcinoma (npc). we used a metabolomics approach to investigate ebv-modulated metabolic changes, and found that the exogenous overexpression of the ebv-encoded latent membrane protein 1 (lmp1) significantly increased glycolysis. the deregulation of several glycolytic genes, including hexokinase ...201424662831
exosomal hif1α supports invasive potential of nasopharyngeal carcinoma-associated lmp1-positive exosomes.it has emerged recently that exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. however, whether oncogenic transcription factors are transduced by exosomes is unknown. hypoxia-inducible factor-1α (hif1α) transcriptionally regulates numerous key aspects of tumor development and progression by promoting a more aggressive tumor phenotype, characterized by increased proliferation and invasiveness coupled with neoangiogenesis. it has been shown that the princi ...201424662828
[epstein-barr virus in the pathogenesis of multiple sclerosis (a review)].multiple sclerosis is now regarded as a disease, which is based on genetic predisposition. trigger mechanism are various exogenous factors. the epstein-barr virus is thought to be a trigger. this report provides information about possible mechanisms of the influence of the epstein-barr virus on the development of multiple sclerosis.201424662354
epstein-barr virus-infected cells in igg4-related lymphadenopathy with comparison with extranodal igg4-related disease.igg4-related lymphadenopathy with increased numbers of epstein-barr virus (ebv)-infected cells has been reported but not fully described. we analyzed 31 cases of igg4-related lymphadenopathy and 24 cases of extranodal igg4-related diseases for their possible relationship with ebv. other types of reactive lymph nodes (22) and angioimmunoblastic t-cell lymphoma (aitl) (10) were also studied for comparison. ebv-encoded rna (eber) in situ hybridization revealed eber(+) cells in 18 of 31 cases (58%) ...201424705309
nuclear translocation and regulation of intranuclear distribution of cytoplasmic poly(a)-binding protein are distinct processes mediated by two epstein barr virus proteins.many viruses target cytoplasmic polya binding protein (pabpc) to effect widespread inhibition of host gene expression, a process termed viral host-shutoff (vhs). during lytic replication of epstein barr virus (ebv) we observed that pabpc was efficiently translocated from the cytoplasm to the nucleus. translocated pabpc was diffusely distributed but was excluded from viral replication compartments. vhs during ebv infection is regulated by the viral alkaline nuclease, bglf5. transfection of bglf5 ...201424705134
determination of ebv serostatus prior to kidney transplantation: comparison of vidas®, liaison® and immunofluorescence assays.immunosuppression following solid organ transplantation reduces t cell-mediated immune control of epstein-barr virus (ebv), which may then drive development of post-transplant lymphoproliferative disease. serology plays a key role in determination of risk of outgrowth of such lesions following transplantation. the study compared the vidas(®) (biomérieux) and liaison(®) (diasorin) enzyme immunoassays (eias) and immunofluorescence assays (ifa; mbl-bion) in the kidney transplantation setting. sera ...201424704349
capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κb-induced matrix metalloproteinase 2 expression.calpain small subunit 1 (capn4) plays a key role in tumor migration or invasion. in this study, expression and function of capn4 was investigated in human nasopharyngeal carcinoma (npc). here we report that both mrna and protein levels of capn4 were elevated in npc tissues when compared to normal np tissues. similarly, capn4 was also highly expressed in multiple npc cell lines, compared to immortalized human nasopharyngeal epithelial cell line np69. moreover, expression of capn4 was significantl ...201424703594
hypoxia-inducible factor 1 and its role in viral carcinogenesis.the advent of modern molecular biology has allowed for the discovery of several mechanisms by which oncoviruses promote carcinogenesis. remarkably, nearly all human oncogenic viruses increase levels of the transcription factor hypoxia-inducible factor 1 (hif-1). in this review, we highlight hif-1׳s significance in viral oncogenesis, while providing an in-depth analysis of its activation mechanisms by the following oncoviruses: human papillomaviruses (hpvs), hepatitis b/c viruses (hbv/hcvs), epst ...201424698149
clinicopathologic, immunophenotypic, and eber in situ hybridization study of extranodal natural killer/t-cell lymphoma, nasal type in ãmulti-ethnic groups.extranodal nasal-type nk/t-cell lymphoma (enktcl) is a common and geographic predominant disease in china. we observed the clinical and pathologic features of this tumor type and its relationship to epstein-barr virus (ebv), and focused on the epidermology and prevalence of enktcl in xinjiang, in order to improve the diagnostic and differential diagnosis ability.201424697118
ct features and pathologic characteristics of lymphoepithelial carcinoma of salivary glands.to investigate and analyze the typical ct findings of salivary gland lymphoepithelial carcinoma.201424696717
editorial commentary: genetics and infectious mononucleosis. 201424696239
a genetic basis for infectious mononucleosis: evidence from a family study of hospitalized cases in denmark.circumstantial evidence from genome-wide association and family studies of various epstein-barr virus-associated diseases suggests a substantial genetic component in infectious mononucleosis (im) etiology. however, familial aggregation of im has scarcely been studied.201424696238
evaluation and management of neck masses in children.neck masses in children usually fall into one of three categories: developmental, inflammatory/reactive, or neoplastic. common congenital developmental masses in the neck include thyroglossal duct cysts, branchial cleft cysts, dermoid cysts, vascular malformations, and hemangiomas. inflammatory neck masses can be the result of reactive lymphadenopathy, infectious lymphadenitis (viral, staphylococcal, and mycobacterial infections; cat-scratch disease), or kawasaki disease. common benign neoplasti ...201424695506
developing a potentially immunologically inert tetracycline-regulatable viral vector for gene therapy in the peripheral nerve.viral vector-mediated gene transfer of neurotrophic factors is an emerging and promising strategy to promote the regeneration of injured peripheral nerves. unfortunately, the chronic exposure to neurotrophic factors results in local trapping of regenerating axons or other unwanted side effects. therefore, tight control of therapeutic gene expression is required. the tetracycline/doxycycline-inducible system is considered to be one of the most promising systems for regulating heterologous gene ex ...201424694534
[primary cns lymphoma--an update].primary central nervous system lymphomas (pcnsl) in immunocompetent patients have long suffered from their rarity. biological studies as well as initiation of comparative prospective therapeutic studies have been delayed in this population. a significant improvement in survival was observed when radiotherapy was preceded by chemotherapy with high dose methotrexate (mtx). median survival improved from 16 months, with radiotherapy alone, to 35-45 months with combined treatments, at the cost of a r ...201424691194
primary epstein-barr virus infection diffusing f18-fluorodeoxyglucose-positron emission tomography/computed tomography response monitoring of hodgkin's disease: a case report.hodgkin's disease is highly curable by radiotherapy and/or chemotherapy, but refractory disease or early relapses are rarely cured by conventional salvage therapy.201424950966
secondary diffuse large b-cell lymphoma after chemotherapy for acute myeloid leukemia: looking for the unexpected diagnosis.development of epstein-barr virus (ebv) positive lymphoproliferative disorders in patients with immunosuppression has become more frequently reported. a patient with acute myeloid leukemia was treated to remission, when on follow-up 9 months after his initial diagnosis, he was noted to have a generalized rash and lymphadenopathy. evaluation of skin and bone marrow biopsies was suggestive of a relapsed leukemia, and treatment was initiated. fever evaluation revealed a high load of ebv in his bloo ...201424950422
a computationally designed inhibitor of an epstein-barr viral bcl-2 protein induces apoptosis in infected cells.because apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. this includes the epstein-barr virus (ebv) gene bhrf1, a homolog of human bcl-2 proteins that block apoptosis and are associated with cancer. computational design and experimental optimization were used to generate a novel protein called bindi that binds bhrf1 with picomolar affinity. bindi recognizes the hydrophobic cleft of bhrf1 in a manner similar to other bc ...201424949974
[some aspects of the treatment of adult patients with epstein-barr virus infection].the review analyzes the basic aspects of treatment policy in patients with different forms of epstein-barr virus infection. practical recommendations are given on the basis of the extensive literature data published in the past 20 years.201424754076
long-term outcome after haploidentical stem cell transplant and infusion of t cells expressing the inducible caspase 9 safety transgene.adoptive transfer of donor-derived t lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-hsct) without the risk for uncontrolled graft versus host disease (gvhd). thus, patients who develop gvhd after infusion of allodepleted donor-derived t cells expressing an inducible human caspase 9 (ic9) had their disease effectively controlled by a single administration of a small-molecule drug (ap1903) tha ...201424753538
risk of diffuse large b-cell lymphoma after solid organ transplantation in the united states.non-hodgkin lymphoma arising in the context of immunosuppression is an important adverse outcome after solid organ transplantation. diffuse large b-cell lymphoma (dlbcl) is the most commonly diagnosed subtype of post-transplantation non-hodgkin lymphoma, but few studies of transplant recipients have examined subtype-specific risks. therefore, we examined dlbcl risk in the transplant cancer match study, including registry-based cancer ascertainment among 96,615 solid organ transplants performed f ...201424753070
new brain lesions in a patient with sarcoidosis: is it neurosarcoidosis?a 45-year-old woman with pulmonary sarcoidosis diagnosed 5 years previously, who was on treatment with prednisone and methotrexate for 1year, developed partial seizure with secondary generalization. mri showed three non-cavitary enhancing lesions in the cerebello-occipital region. these lesions were presumed to be neurosarcoidosis. methotrexate was discontinued, prednisone dose was increased and azathiopurine and levetiracetam were added. while on treatment, follow up imaging showed enlarging br ...201424751455
mcaf1 and rta-activated bzlf1 transcription in epstein-barr virus.epstein-barr virus (ebv) expresses two transcription factors, rta and zta, which are involved in the transcriptional activation of ebv lytic genes. this study sought to elucidate the mechanism by which rta activates transcription of the zta-encoding gene, bzlf1, through the zii element in the gene promoter. in a dna affinity precipitation assay, atf2 was found to associate with an rta-interacting protein, mcaf1, at the zii element. the interaction between rta, mcaf1, and atf2 at the same site in ...201424598729
t-cell therapy using a bank of ebv-specific cytotoxic t cells: lessons from a phase i/ii feasibility and safety study.we report herein the results we obtained and the limitations we experienced during the production and use of a bank of epstein-barr virus (ebv)-transformed human cytotoxic t lymphocytes (ebv-ctls). to assess the feasibility and toxicity of this strategy, we selected and stored, in liquid nitrogen, 4 billion ebv-ctls from each of the 13 selected donors. subsequently, in a multicenter phase i/ii study, 11 patients with ebv-associated lymphoma resistant to conventional treatments received 1-3 doses ...201424598452
human papillomavirus and epstein barr virus in head and neck carcinomas: suggestions for the new who classification.in the 9 years since the last world health organization (who) classification for head and neck tumors, a great deal has changed. in particular, human papillomavirus (hpv) has emerged as the major etiologic agent and patient prognostic marker for squamous cell carcinoma, most profoundly in the oropharynx. it also casts a long shadow over all of the rest of head and neck cancer given its biologic and prognostic implications. by contrast, little has changed regarding our knowledge of epstein-barr v ...201424595417
comparison of clinical features and ebv expression in histiocytic necrotizing lymphadenitis of children and adults.histiocytic necrotizing lymphadenitis (hnl) is a self-limiting disease characterized by cervical lymphadenopathy and fever. epstein-barr virus (ebv) has been implicated as a cause of hnl in some reports but not in others. the aim of this study was to compare the clinical features and laboratory findings in children and adults with hnl and to evaluate the relationship between ebv infection and hnl.201424594231
inflammatory pseudotumor of spleen.inflammatory pseudotumor (ipt) is an uncommon tumor and its occurrence in spleen is rare. this tumor is composed of proliferation of spindle cells of unknown origin and etiology that mimic other tumors at clinical and histological evaluation. the most surmising etiology is epstein barr virus (ebv) and the most suspected origin is myofibroblasts, hence its synonym is "inflammatory myofibroblastic tumor." the clinical appearance of tumor is related to its location but the most ones are abdominal p ...201424592376
primary hodgkin lymphoma of the central nervous system.primary involvement of the central nervous system by hodgkin lymphoma is rare; most cases represent metastases. we report a primary hodgkin lymphoma presenting in the cerebellum of a 77-year-old man and review the literature on primary hodgkin lymphoma of the central nervous system.201424589557
cellular immune controls over epstein-barr virus infection: new lessons from the clinic and the laboratory.epstein-barr virus (ebv), a human herpesvirus with potent b cell growth transforming ability, induces multiple cellular immune responses in the infected host. how these host responses work together to prevent virus pathogenicity, and how immune imbalance predisposes to disease, remain poorly understood. here, we describe three ongoing lines of enquiry that are shedding new light on these issues. these focus on: (i) patients with infectious mononucleosis or its fatal equivalent, x-linked lymphopr ...201424589417
role of the histone h3 lysine 9 methyltransferase suv39 h1 in maintaining epsteinn-barr virus latency in b95-8 cells.the ability of epstein-barr virus (ebv) to establish latent infection is associated with infectious mononucleosis and a number of malignancies. in ebv, the product of the bzlf1 gene (zebra) acts as a master regulator of the transition from latency to the lytic replication cycle in latently infected cells. ebv latency is primarily maintained by hypoacetylation of histone proteins in the bzlf1 promoter by histone deacetylases. although histone methylation is involved in the organization of chromat ...201424588869
specific aspects of modern life for people with multiple sclerosis: considerations for the practitioner.multiple sclerosis (ms) is a chronic, debilitating, neurodegenerative disease that has a high impact on patients' quality of life. individuals are often diagnosed in early adulthood and are faced with the difficulty of managing their lifestyle within the context of this chronic illness. here we review factors that influence the disease course and the challenges that might be encountered when managing patients with ms. the majority of diagnosed patients are women of childbearing age, making pregn ...201424587828
transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.although the most common clinical presentation of multiple sclerosis (ms) is the so called relapsing-remitting ms (rrms), the molecular mechanisms responsible for its progression are currently unknown. to tackle this problem, a whole-genome gene expression analysis has been performed on rrms patients.201424587374
rna compass: a dual approach for pathogen and host transcriptome analysis of rna-seq datasets.high-throughput rna sequencing (rna-seq) has become an instrumental assay for the analysis of multiple aspects of an organism's transcriptome. further, the analysis of a biological specimen's associated microbiome can also be performed using rna-seq data and this application is gaining interest in the scientific community. there are many existing bioinformatics tools designed for analysis and visualization of transcriptome data. despite the availability of an array of next generation sequencing ...201424586784
the epstein-barr virus-encoded microrna mir-bart9 promotes tumor metastasis by targeting e-cadherin in nasopharyngeal carcinoma.micrornas (mirnas) are a family of small rna molecules that negatively regulate the expression of protein-coding genes and play critical roles in orchestrating diverse cellular processes. this regulatory mechanism is also exploited by viruses to direct their life cycle and evade the host immune system. epstein-barr virus (ebv) is an oncogenic virus that is closely associated with multiple human diseases, including nasopharyngeal carcinoma (npc), which is a highly metastatic type of tumor and is ...201424586173
epstein-barr virus large tegument protein bplf1 contributes to innate immune evasion through interference with toll-like receptor signaling.viral infection triggers an early host response through activation of pattern recognition receptors, including toll-like receptors (tlr). tlr signaling cascades induce production of type i interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. to allow infection, replication, and persistence, (herpes)viruses employ ingenious strategies to evade host immunity. the human gamma-herpesvirus epstein-barr virus (ebv ...201424586164
increased incidence of adenoidectomy and tonsillectomy in children with renal transplantation.previous studies have found that pediatric solid organ transplant recipients suffer from adenotonsillar hyperplasia. however, as this condition is also common in normal children, it remains unclear whether the incidence is truly increased. the aim of this study was to compare the incidences of surgery on the adenoids and tonsils of normal children with those receiving renal transplants and to define risk factors in the transplant population.201424584665
hematopoietic stem cell transplantation conditioning with use of rituximab in ebv related lymphoproliferative disorders.x-linked lymphoproliferative disease (xlp) and il-2-inducible t cell kinase (itk) deficiency are rare immunodeficiencies with a spectrum of clinical manifestations. although there are no official guidelines for allogeneic hematopoietic stem cell transplantation (hsct) in these patients, previous reports have shown that reduced intensity conditioning regimens provide successful engraftment with limited toxicity. here, we report on three children with xlp and one with itk deficiency, who underwent ...201424584040
prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large b-cell lymphoma in western countries.epstein-barr virus-positive (ebv(+)) diffuse large b-cell lymphoma (dlbcl) of the elderly is a variant of dlbcl with worse outcome that occurs most often in east-asian countries and is uncommon in the western hemisphere. we studied the largest cohort of ebv(+) dlbcl, independent of age, treated with rituximab combined with chop (r-chop) in developed western countries.201424583797
gene expression profiling of epstein-barr virus-positive diffuse large b-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways.epstein-barr virus (ebv)-positive diffuse large b-cell lymphoma (dlbcl) of the elderly (ebv[+]dlbcl-e) is classified as a subtype of dlbcl. until now, its molecular pathogenesis has remained unknown. to identify pathways characteristic of ebv(+)dlbcl-e, gene expression profiling of five ebv(+)dlbcl-e and seven ebv-negative dlbcl (ebv[-]dlbcl) cases was undertaken using human oligonucleotide microarray analysis. gene set enrichment analysis and gene ontology analysis showed that gene sets of the ...201424581222
modes of infection and oncogenesis by the epstein-barr virus.the ebv is a human γ-herpesvirus associated with various neoplasms. it is responsible for causing cancers of b, t, and nk cells as well as cells of epithelial origin. such diversity in target cells and the complicated steps of oncogenesis are perplexing when we speculate about the mechanisms of action of ebv-positive cancers. here, we first note three common features that contribute to the development and maintenance of ebv-positive cancers: effects of ebv oncogenes, immunosuppression and evasio ...201424578255
review: an exposition of medicinal preponderance of moringa oleifera (lank.).medicinal plants are believed to be a precious natural reservoir as they are assumed to have paranormal effects for the mankind. moringa oleifera grows throughout most of the tropics and has numerous industrial and medicinal uses. this review acquaints with the consequence of fera (moringaceae), a fast growing medicinal plant wide spread in tropical regions with height ranging from 5-10m. it has an enormous nutritional worth due to existence of vitamins and proteins. it is subsisted with many co ...201424577932
hla-drb1 15:01 and epstein-barr virus in a multiple sclerosis patient with psoriasis, nasopharyngeal and breast cancers. lessons for possible hidden links for autoimmunity and cancer.multiple sclerosis (ms) patients have a low general cancer risk and cases of neoplastic comorbidity are attributed by many researchers in chance, or therapeutical side-effects. human leucocyte antigen (hla) class ii allele drb1 15:01 is considered the main genetic factor independently associated with increased susceptibility for ms in caucasians. epstein-barr virus (ebv) has also been proven to be a core triggering factor in ms initiation and progress, mainly in hla-drb1 15:01 positive ms patien ...201424576802
a rare case of undifferentiated nonkeratinizing carcinoma of the lip mucosa.undifferentiated nonkeratinizing carcinoma (unc) is a poorly differentiated squamous cell carcinoma accompanied by a prominent reactive lymphoplasmacytic infiltrate that can occur in many anatomic sites. it shares morphologic features with undifferentiated nonkeratinizing nasopharyngeal carcinoma, in which a strong association with epstein-barr virus (ebv) has been noted. among uncs arising outside the nasopharynx, the linkage with ebv is variable; in particular, the few cases of unc of the lip ...201424576436
epstein-barr virus infection in children with renal transplantation: 17 years experience at a single center.the aim of this study was to detect the frequency, time of occurrence, management and outcome of epstein-barr virus (ebv) infection and related complications in pediatric renal transplant recipients.201424575865
epstein-barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: case series.epstein-barr virus (ebv)-associated lymphoepithelioma-like gastric carcinoma (lelc) is characterized by a lower lymph node (ln) metastasis rate and a higher survival rate than other forms of gastric cancer. although current prognosis for lelc is favorable, the most common approach is radical gastrectomy involving an extensive d2 lymph node dissection. here, we report four cases of ebv-associated early lelc that were treated by an alternative approach, endoscopic submucosal dissection (esd). the ...201424574813
comparison of two laboratory extraction techniques for the detection of epstein-barr virus in the saliva of nasopharyngeal carcinoma patients.the aim of the present study was to compare the effectiveness of dna extraction using an extraction kit against the standard boiling technique for the detection of epstein-barr virus (ebv) dna in nasopharyngeal carcinoma (npc) patients.201424574317
epstein-barr virus and telomerase: from cell immortalization to therapy.overcoming cellular senescence is strictly required for virus-driven tumors, including those associated with epstein-barr virus (ebv). this critical step is successfully accomplished by ebv through tert expression and telomerase activation in infected cells. we herein review the complex interplay between ebv and tert/telomerase in ebv-driven tumorigenesis. evidence accumulated so far clearly indicates that elucidation of this issue may offer promising opportunities for the design of innovative t ...201424572088
the epstein-barr virus causes epithelial-mesenchymal transition in human corneal epithelial cells via syk/src and akt/erk signaling pathways.although epstein-barr virus (ebv)-associated keratitis is rare, it can cause acute corneal necrosis and neovascularization. we aimed to examine the signaling mechanism by which ebv causes epithelial-mesenchymal transition (emt) in human corneal epithelial cells (hcecs) in vitro.201424569586
cerebral vasculitis and encephalitis due to epstein-barr virus in a patient with newly diagnosed hiv infection.epstein-barr virus (ebv) is a common infection which usually produces mild or no symptoms in immunocompetent individuals. in human immunodeficiency virus (hiv) associated immunosuppression it is most commonly associated with malignancy which usually occurs at very low cd4+ cell counts. we describe a newly diagnosed hiv-positive patient who presented with headaches and cerebellar signs. she was incorrectly diagnosed with cerebral tuberculosis (tb) infection based on the histology report from a ce ...201424568965
il-1 and tnf-α regulation of aryl hydrocarbon receptor (ahr) expression in hsy human salivary cells.recent findings demonstrate that nuclear receptor - aryl hydrocarbon receptor (ahr) may play an important role in the pathogenesis of sjögren's syndrome (ss) via involvement in epstein-barr virus reactivation. in that study a reporter system was used. therefore, it was decided to define ahr expression in human salivary cell line (hsy) and its functional regulators.201424565903
composite lymphoid neoplasm of b-cell and t-cell origins: a pathologic study of 14 cases.we retrospectively analyzed 14 composite lymphoma/lymphoid neoplasms (cl) of b-cell/t-cell origins. these consisted of a spectrum of t-cell neoplasms in combination with different b-cell lymphomas/leukemias, with peripheral t-cell lymphoma and diffuse large b-cell lymphoma encountered most frequently for each respective neoplastic lineage. histopathologic evaluation demonstrated 6 patterns of neoplastic distribution, including zone, inverted zone, diffuse mixed, regional/nodular mixed, compartme ...201424565206
a yeast-based assay identifies drugs that interfere with immune evasion of the epstein-barr virus.epstein-barr virus (ebv) is tightly associated with certain human cancers, but there is as yet no specific treatment against ebv-related diseases. the ebv-encoded ebna1 protein is essential to maintain viral episomes and for viral persistence. as such, ebna1 is expressed in all ebv-infected cells, and is highly antigenic. all infected individuals, including individuals with cancer, have cd8(+) t cells directed towards ebna1 epitopes, yet the immune system fails to detect and destroy cells harbor ...201424558096
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