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the transcription factor hobit identifies human cytotoxic cd4(+) t cells.the t cell lineage is commonly divided into cd4-expressing helper t cells that polarize immune responses through cytokine secretion and cd8-expressing cytotoxic t cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. recently, a population of cd4(+) t cells that conforms to the phenotype of cytotoxic cd8(+) t cells has received increased recognition. these cytotoxic cd4(+) t cells display constitutive expression of granzyme b and perforin at the protein leve ...201728392788
herpesviruses hijack host exosomes for viral pathogenesis.herpesviruses are remarkable pathogens possessing elaborate mechanisms to seize various host cellular components for immune evasion, replication, and virion egress. as viruses are dependent upon their hosts, investigating this intricate interplay has revealed that the exosome pathway is utilised by alpha (herpes simplex virus 1), beta (human cytomegalovirus, and human herpesvirus 6) and gamma (epstein-barr virus, and kaposi sarcoma-associated herpesvirus) herpesviruses. virions and exosomes shar ...201728456604
histone h4k20 tri-methylation at late-firing origins ensures timely heterochromatin replication.among other targets, the protein lysine methyltransferase pr-set7 induces histone h4 lysine 20 monomethylation (h4k20me1), which is the substrate for further methylation by the suv4-20h methyltransferase. although these enzymes have been implicated in control of replication origins, the specific contribution of h4k20 methylation to dna replication remains unclear. here, we show that h4k20 mutation in mammalian cells, unlike in drosophila, partially impairs s-phase progression and protects from d ...201728778956
the histological and biological spectrum of diffuse large b-cell lymphoma in the world health organization classification.diffuse large b-cell lymphomas (dlbcls) are aggressive b-cell lymphomas that are clinically, pathologically, and genetically diverse, in part reflecting the functional diversity of the b-cell system. the focus in recent years has been toward incorporation of clinical features, morphology, immunohistochemistry, and ever evolving genetic data into the classification scheme. the 2008 world health organization classification reflects this complexity with the addition of several new entities and vari ...201723006945
t-cell lymphoma/sézary syndrome in a liver transplant recipient.cutaneous t-cell lymphoma is a rare subtype of posttransplantation lymphoproliferative disease, with only 29 cases reported in the literature to date, the majority of which are post-renal transplantation. only a few were reported after pancreas, heart, and bone marrow transplantation. there have been no reports of cutaneous t-cell lymphoma following liver transplantation to date.201722418000
intravascular large b-cell lymphoma: a difficult diagnostic challenge.case presentation. a 69-year-old hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. hemoglobin was 6.7, prothrombin time (pt) 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (ptt) 55.6 seconds, fibrin split 10 µg/l, and lactate dehydrogenase (ldh) 1231 ...201726425595
molecular mimicry of mage-a6 and mycoplasma penetrans hf-2 epitopes in the induction of antitumor cd8(+) t-cell responses.a promising vaccine strategy for the treatment of cancer involves the use of vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific cd4(+) and cd8(+) t-cells. previously, we reported that a mage-a6-derived peptide (mage-a6172-187) and its highly-immunogenic and cross-reactive homolog derived from mycoplasma penetrans hf-2 permease (hf-2216-229) are promiscuously presented by multiple hla-dr alleles to responder cd4(+) t-cells obtained from ...201725960935
role of infectious agents in cutaneous t-cell lymphoma: facts and controversies.the etiology of cutaneous t-cell lymphoma (ctcl) remains unknown, with potential infectious causes having been explored. this contribution evaluates the evidence suggesting an infectious etiology and pathogenesis of the disease, characterizes the relationships between various specific pathogens and ctcl, and discusses some of the difficulties in establishing a causal link between infectious agents and ctcl carcinogenesis. researchers have evaluated ctcl specimens for evidence of infection with a ...201723806159
epstein -barr virus association with malignant lymphoma subgroups in zaria, nigeria.epstein-barr virus (ebv) is said to infect more than 90% of humans worldwide with latent infection for life. a recognized carcinogen, ebv is linked to malignant lymphoma (ml) subtypes of burkitt's lymphoma (bl), plasmablastic lymphoma, diffuse large cell lymphoma (dlbcl) and hodgkin's lymphoma (hl). we report the association of ebv with ml in a segment of our patient population. paraffin blocks from the archives of abuth, zaria were used to construct tissue microarray sections stained using 30 m ...201725620871
cytokeratin-negative undifferentiated (lymphoepithelial) carcinoma of the lacrimal sac.epstein-barr virus-associated undifferentiated (lymphoepithelial) carcinoma is a malignancy that most commonly arises in the nasopharynx but can also occur in other locations including the lacrimal sac. generally, this tumor strongly expresses cytokeratin, making the diagnosis straightforward. in the absence of confirmatory immunohistochemistry, the diagnosis can be problematic, particularly for tumors arising in unusual locations. only 3 cases arising in the lacrimal sac in association with eps ...201725719371
angioimmunoblastic t-cell lymphoma: a diagnostic challenge.angioimmunoblastic t-cell lymphoma (aitl) accounts for 15-20% of all peripheral t-cell lymphomas. it is a rare subtype of cd4 t-cell peripheral lymphoma that affects aged individuals, causing b symptoms, generalized lymphadenopathy and hepatosplenomegaly. its pathogenesis is still unclear, but in some cases it has been associated with infection, allergic reaction or drug exposure. the majority of patients are diagnosed in an advanced stage and anthracycline based regimen is considered the first- ...201725685133
[macrophage activation syndrome in a patient with systemic juvenile idiopathic arthritis].machrophage activation syndrome (mas) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. it is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia ...201725575650
hemophagocytic lymphohistiocytosis secondary to epstein barr virus and leishmania co-infection in a toddler.this is the report of an ebv+leishmanial co-infection. the patient developed hemophagocytic syndrome (hlh) and was treated with the standard hlh-2004 protocol. however, pcr in bone marrow discovered this secondary cause for hlh. in endemic countries, visceral leishmaniasis should be considered in the differential diagnosis even in ebv-related hlh, as chemotherapy toxicity may be avoided.201725511219
hepatosplenic hodgkin lymphoma without lymphadenopathy following reversible methotrexate-associated lymphoproliferative disorder.lymphoproliferative disorders (lpds) occur more frequently in rheumatoid arthritis (ra) patients treated with immunosuppressive agents than in the non-ra population. however, the various forms of disease progression have not yet been elucidated in detail. we encountered a case of epstein-barr virus (ebv)-positive atypical polymorphous lpd in the cervical and intraabdominal lymph nodes with hepatosplenomegaly in an 88-year-old female with ra who had taken infliximab and methotrexate (mtx) for six ...201725401225
ebv-associated lymphoepithelioma-like carcinoma of the pancreas: case report with targeted sequencing analysis.lymphoepithelioma-like carcinomas are distinctive epithelial derived malignant neoplasms that have a syncytial growth pattern and lymphoid stroma. the majority of tumors with this appearance are epstein barr virus (ebv)-associated. we report a patient with a clinical presentation concerning for lymphoma who was diagnosed with an ebv-associated pancreatic carcinoma with a lymphoepithelioma-like pattern. targeted sequencing analysis showed a molecular profile distinct from conventional ductal aden ...201725922198
toll-like receptor gene polymorphisms and susceptibility to epstein-barr virus-associated and -negative gastric carcinoma in northern china.various polymorphisms in toll-like receptor (tlr) genes have been identified and associated with susceptibility to various malignancies, such as gastric carcinoma (gc), breast cancer, and prostate cancer. however, little is known about the polymorphisms of tlr genes and the susceptibility to gc in northern china, especially to epstein-barr virus-associated gc (ebvagc). we focused on the association with susceptibility to gc, especially to ebvagc.201725843196
extranodal nk/t-cell lymphoma mimicking erythema multiforme.extranodal natural killer/t-cell lymphoma (enktl) is an extremely rare and an aggressive lymphoma. we report an interesting case of extranodal natural killer/t-cell lymphoma in a middle-aged woman which mimicked erythema multiforme. the skin lesions of this case looked like erythema multiforme due to the tagetoid lesions and mucosal erosions. the two biopsies from her chest and scalp lesions were different. one exhibited the characteristics of cd4+ cd56+ cd8-mycosis fungoides whereas the other b ...201726120182
evaluation of the association between epstein-barr virus and mycosis fungoides.mycosis fungoides (mf) is the most common cutaneous t-cell lymphomas. despite extensive studies, etiopathogenesis of mf is unknown. environmental, infectious and genetic factors have been proposed as potential risk factors of mf. herpes virus family members, especially epstein-barr virus (ebv), have been among the viral factors of interest in recent years. the aim of this study was to investigate the possible association of ebv infection with mf.201726120176
the prognostic significance of ebv dna load and eber status in diagnostic specimens from diffuse large b-cell lymphoma patients.epstein-barr virus (ebv)-encoded small rna in situ hybridization (eber-ish) is a widely accepted method to evaluate ebv involvement in diffuse large b-cell lymphoma (dlbcl), although little is known regarding associations between ebv dna load and the eber status and whether ebv dna load data provide additional clinical information. in this study, we quantified ebv dna load in diagnostic specimens from dlbcl patients diagnosed at our hospital to evaluate clinical implications of ebv dna load in d ...201726177728
optic neuritis following epstein-barr virus encephalitis in immunocompetent children: a case report. 201726073488
candidate gene association studies and risk of hodgkin lymphoma: a systematic review and meta-analysis.to evaluate the contribution of association studies of candidate polymorphisms to inherited predisposition to hodgkin lymphoma (hl), we conducted a systematic review and meta-analysis of published case-control studies. of the variants examined more than once in candidate gene association studies, we identified 21 studies that reported on 12 polymorphic variants in 10 genes. data were also extracted from a published genome wide association study to allow analysis of an additional 47 variants in a ...201726053036
interferon beta-1a treatment in htlv-1-associated myelopathy/tropical spastic paraparesis: a case report.here a young patient (< 21 years of age) with a history of infective dermatitis is described. the patient was diagnosed with myelopathy associated with htlv-1/tropical spastic paraparesis and treated with interferon beta-1a. the disease was clinically established as htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp), and laboratory tests confirmed the presence of antibodies to htlv-1 in the cerebrospinal fluid (csf). mumps, cytomegalovirus, epstein-barr virus, schistosomiasis, h ...201725229227
tracheal epstein-barr virus-associated smooth muscle tumour in an hiv-positive patient.epstein-barr virus-related smooth muscle tumours (ebv-smts) are a rare but well recognized non-aids-defining malignancy that can also be found in several other immunosuppressed states. pulmonary involvement of ebv-smts is not uncommon, but it can present with multifocal lesions in any anatomical site. the present article describes an hiv-positive woman with dyspnea who was found to have a large tracheal ebv-smt. the authors discuss their approach to diagnosis and management, and present unique f ...201725255459
a case of mature natural killer-cell neoplasm manifesting multiple choroidal lesions: primary intraocular natural killer-cell lymphoma.natural killer (nk) cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. it usually emerges from the nose and appears in the ocular tissue as a metastasis. herein, we describe a case of nk-cell neoplasm in which the eye was considered to be the primary organ.201726668579
nhl - extranodal t-cell lymphoma.extranodal nk/t-cell lymphoma, nasal type (enkl) is a rare lymphoid neoplasm that in the past has been grouped with a variety of granulomatous diseases. enkl occurs in all age groups. however, it seems to occur more often in people in their 50s and affects more men than women. it is strongly linked to the epstein-barr virus (ebv), especially in people of asian countries. because this type of lymphoma occurs in organs or tissues other than lymph nodes, it is called enkl. this is a case report of ...201726668464
molecular concept in human oral cancer.the incidence of oral cancer remains high in both asian and western countries. several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. oral squamous carcinogenesis is a multistep process in wh ...201726668446
lymphoepithelioma-like carcinoma of the urinary bladder: a rare case report.bladder cancers are the second most common urogenital malignancy, its most common type being urothelial carcinoma. lymphoepithelioma-like carcinoma (lelc) which is commonly described in the nasopharynx is a very rare presentation in the bladder. diagnosis of this entity poses a histopathological challenge. nonetheless, the correct diagnosis is important as it implies a different therapeutic approach with the potential bladder salvage treatment protocol. we here present a case of an 87-year-old m ...201726692678
rampant infections of bone marrow stem cell niches as triggers for spondyloarthropathies and rheumatoid arthritis.tropheryma whipplei can induce rheumatism mimicking spa or ra, but even more rampant bacterial/viral infections in epiphyseal bones could also contribute to the onset of ra and spa. indeed, as bone marrow stem cell niches are enriched in tregs and myeloid derived suppressor cells, these areas are favourable for the persistence of quiescent viruses and/or dormant bacteria. this review focuses on the possibility that such silent infections of bone marrow stem cell niches might contribute to the pa ...201726886813
weathering a cytokine storm: a case of ebv-induced hemophagocytic lymphohistiocytosis.hemophagocytic lymphohistiocytosis (hlh) is a rare but life-threatening disease caused by excessive immune activation. acquired hlh is seen in adults and is often caused by infection or malignancy. diagnosis is difficult and usually missed as clinical and laboratory findings are nonspecific. moreover, the pathophysiology of the systemic inflammatory response syndrome and/or sepsis is remarkably similar to hlh. thus, in patients presenting with presumed severe sepsis or septic shock complicated b ...201727200381
role of human papillomavirus and tumor suppressor genes in oral cancer.the incidence of oral cancer remains high and is associated with many deaths in both western and asian countries. several risk factors for the development of oral cancer are now well known, including smoking, drinking and consumption of smokeless tobacco products. genetic predisposition to oral cancer has been found in certain cases, but its components are not yet entirely clear. in accordance with the multi-step theory of carcinogenesis, the natural history of oral cancer seems to gradually evo ...201727194871
patterns of pd-l1 expression and cd8 t cell infiltration in gastric adenocarcinomas and associated immune stroma.recent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. here, we evaluate gastric and gastro-oesophageal junction (g/gej) adenocarcinomas for their expression of programmed death-ligand 1 (pd-l1), infiltration by cd8+ t cells and the relationship of both factors to patient survival.201726801886
bart mirnas: an unimaginable force in the development of nasopharyngeal carcinoma.nasopharyngeal carcinoma (npc) is a head and neck cancer that represents a major health burden in southern china and southeast asia. although the close association of npc with epstein-barr virus (ebv) infection has been demonstrated, its exact role in the pathogenesis of this malignancy is still unclear. the expression of ebv-encoded micrornas, especially bart mirnas, which are encoded from the bamhi-a region of the viral genome, is detected at a high level in npc. mirnas are small noncoding mrn ...201726909566
epstein-barr virus encephalitis with substantia nigra involvement.infectious mononucleosis due to epstein-barr virus (ebv) is a usually benign systemic viral illness common in children. many studies described nervous system manifestations of infectious mononucleosis with a wide spectrum of neurologic deficits. neurologic complications of ebv are seen in both acute and reactivate infection. herein, we describe a patient diagnosed by acute ebv encephalitis with substantia nigra involvement and excellent clinical recovery.201726962357
iatrogenic immunodeficiency-associated lymphoproliferative disorders in transplant and nontransplant settings.iatrogenic immunodeficiency-associated lymphoproliferative disorders comprise a group of lymphoid neoplasms that are associated with an immunosuppressed state, either in the posttransplant period, or during the treatment of various autoimmune and rheumatologic disorders by immunomodulatory medications. their morphologies vary widely but are generally classified according to the lymphomas that they most closely resemble. this group is strongly associated with infections by the epstein-barr virus ...201726960627
neurosurgery and human immunodeficiency virus in the era of combination antiretroviral therapy: a review.human immunodeficiency virus (hiv) is a global health problem. it renders the central nervous system susceptible to infectious and noninfectious diseases. hiv-positive individuals may present to neurosurgical services with brain lesions of unknown etiology. the differential diagnosis in these cases is broad, including opportunistic infections and malignancies, and investigation should be tailored accordingly. opportunistic infections of the central nervous system can be complicated by hydrocepha ...201727081898
ebv-associated peripheral t-cell lymphoma of gastrointestinal tract presented with widespread chronic inflammation: a case report.we report a case of epstein-barr virus (ebv)-associated t-cell lymphoma of gastrointestinal (gi) tract from a 70-year-old white woman who initially presented with a widespread gi inflammation and gastric obstruction. initial biopsies of the gi tract showed severe chronic inflammation in the esophagus, stomach, and the small intestine. celiac disease and inflammatory bowel disease were ruled out. the patient was treated with partial gastrectomy. histology showed gastric wall thickening with ebv-p ...201727093448
epstein-barr virus and its association with rheumatoid arthritis and oral lichen planus.pathogenesis of autoimmune diseases (ad) is one of a multifactorial milieu. a genetic predisposition, an immune system failure, hormonal imbalance and environmental factors play important roles. among the many environmental factors, the role of infection is gaining importance in the pathogenesis of various autoimmune disorders; among them, epstein-barr virus (ebv) plays a pivotal role. literature states an association of various ad with ebv namely multiple sclerosis, autoimmune thyroiditis, syst ...201726980953
extranodal natural killer/t-cell lymphoma, nasal type: a great pretender.extranodal natural killer/t-cell lymphoma, nasal type (enktcl) is a rare epstein-barr virus associated lymphoma seen predominantly in asian population with a 5 years survival rate ranging from 10% to 75% depending on the stage of presentation. in this case report, we describe an unusual presentation of enktcl, which in its early stages was clinically misdiagnosed as buccal space infection and later on histologically as inflammatory myofibroblastic pseudotumor owing to manifold reasons. postopera ...201726539376
cd5-positive primary intraocular b-cell lymphoma arising during methotrexate and tumor necrosis factor inhibitor treatment.to report a case of cd5+ primary intraocular b-cell lymphoma arising during methotrexate (mtx) and tumor necrosis factor (tnf) inhibitor treatment in a young patient with rheumatoid arthritis and uveitis.201726483672
stable persistence of the yeast plasmid by hitchhiking on chromosomes during vegetative and germ-line divisions of host cells.the chromosome-like stability of the saccharomyces cerevisiae plasmid 2 micron circle likely stems from its ability to tether to chromosomes and segregate by a hitchhiking mechanism. the plasmid partitioning system, responsible for chromosome-coupled segregation, is comprised of 2 plasmid coded proteins rep1 and rep2 and a partitioning locus stb. the evidence for the hitchhiking model for mitotic plasmid segregation, although compelling, is almost entirely circumstantial. direct tests for plasmi ...201726442178
joint involvement secondary to epstein-barr virus.we describe a group of patients with epstein-barr virus (ebv) infection and joint involvement. between february 2011 and january 2012, there were six cases in our unit. two presented with a pattern similar to rheumatoid arthritis, three had polyarthralgia with an inflammatory pattern and only one patient had asymmetrical oligoarthritis of large joints. they were all women aged between 25 and 75 (4 were of child-bearing potential). diagnosis in all the cases was made by exclusion of other possibl ...201726441062
clinicopathologic characteristics of microsatellite instable gastric carcinomas revisited: urgent need for standardization.microsatellite instable gastric cancer (msi-gc) is a specific molecular subtype of gc. we studied the phenotypes, genotypes, and clinicopathologic characteristics of msi-gc in a white gc cohort and compared our findings with an extended literature review. the study cohort consisted of 482 patients. specimens were available from 452 cases and were used for immunostaining (mlh1, pms2, msh2, msh6) and molecular biological analyses (bat-25, bat-26, nr-21, nr-24, nr-27; epstein-barr virus in situ hyb ...201726371427
the presence of human papillomavirus and epstein-barr virus in male chinese lichen sclerosus patients: a single center study.this study aimed to investigate the presence of human papillomavirus and epstein-barr virus in male lichen sclerosus patients. we extracted dna from formalin-fixed paraffin-embedded foreskin tissue blocks of 47 male ls patients and 30 healthy men and performed real-time pcr test to detect hpv and ebv. none of the 47 ls patients and 30 healthy men had detectable hpv infection. ebv was detected in 18 ls patients (38.3%) and four healthy men (13.3%), the difference is significant (p < 0.05). tissue ...201726289401
epstein-barr virus mrna profiles and viral dna methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin.undifferentiated nasopharyngeal carcinoma (npc) is 100% associated with epstein-barr virus (ebv) as oncogenic driver. npc is often diagnosed late due to initial vague complaints and obscured location. prior studies suggest that measurement of ebv dna load and rna transcripts in nasopharyngeal (np) brushings is useful for minimally invasive npc diagnosis. however, whether these ebv markers relate to local virus replication or reflect tumor origin remains to be demonstrated. to resolve this, we an ...201727600027
clinical outcome and morbidity in pediatric patients with nasopharyngeal cancer treated with chemoradiotherapy.the aim of the study was to evaluate the outcome and treatment-related morbidity in pediatric patients with nasopharyngeal carcinoma (npc) treated with chemoradiotherapy.201727681956
idiopathic nephrotic syndrome: the ebv hypothesis.steroid sensitive nephrotic syndrome is marked by a massive proteinuria and loss of podocytes foot processes. the mechanism of the disease remains debated but recent publications suggest a primary role of epstein-barr virus (ebv). ebv replication in the peripheral blood is found in 50% of patients during the first flare of the disease. the genetic locus of steroid sensitive nephrotic syndrome was also identified as influencing antibodies directed against ebna1. ebv is able to establish, latent b ...201727682967
epstein-barr virus latent membrane protein-1 up-regulates cytokines and correlates with older age and poorer prognosis in hodgkin lymphoma.previously, we reported an association between epstein-barr virus (ebv)-positive hodgkin lymphoma (hl), older age, and poorer prognosis. the aim of this study was to investigate the mechanisms underlying this association.201727632954
ebv-negative aggressive nk-cell leukemia/lymphoma: clinical, pathologic, and genetic features.aggressive natural killer cell leukemia (ankl) is a systemic nk-cell neoplasm, almost always associated with epstein-barr virus (ebv). rare cases of ebv-negative ankl have been described, and some reports suggested more indolent behavior. we report the clinicopathologic, immunophenotypic, and molecular characteristics of 7 ebv-negative ankl. all patients were adults, with a median age of 63 years (range 22 to 83 y) and an m:f ratio of 2.5:1. five patients were white, 1 black, and 1 asian. all pa ...201727631517
hemophagocytic lymphohistiocytosis associated with epstein-barr virus in the central nervous system.hemophagocytic lymphohistiocytosis (hlh) is a rare immune hyperactivation syndrome which may be primary (genetic) or secondary to various immune-related conditions including infection, immunodeficiency, and malignancies. rapid diagnosis and treatment are essential because it can be associated with significant morbidity and mortality. epstein-barr virus (ebv) is a known infectious cause of acquired hlh, but ebv-associated hlh involving the central nervous system is rare and not well characterized ...201727574808
potential interest in circulating mir-bart17-5p as a post-treatment biomarker for prediction of recurrence in epstein-barr virus-related nasopharyngeal carcinoma.epstein-barr virus (ebv)-related micornas (mirnas), bamhi-a rightward transcripts (bart)-mirnas, are released in a stable form from viable cells, which are abundant in patients with ebv-positive nasopharyngeal carcinoma (npc). we estimated copy numbers of circulating mir-bart2-5p, mir-bart17-5p, and mir-bart18-5p as well as bamhi-w dna as biomarkers.201727684719
mutagenesis and genome engineering of epstein-barr virus in cultured human cells by crispr/cas9.the clustered regularly interspaced short palindromic repeats (crispr)-crispr associated protein 9 nuclease (cas9) system is a powerful genome-editing tool for both chromosomal and extrachromosomal dna. dna viruses such as epstein-barr virus (ebv), which undergoes episomal replication in human cells, can be effectively edited by crispr/cas9. we have demonstrated targeted editing of the ebv genome by crispr/cas9 in several lines of ebv-infected cells. crispr/cas9-based mutagenesis and genome engi ...201727709566
the epstein-barr virus dna load in the peripheral blood of transplant recipients does not accurately reflect the burden of infected cells.transplant recipients frequently exhibit an increased epstein-barr virus (ebv) load in the peripheral blood. here, we quantitated the ebv-infected cells in the peripheral blood of these patients and defined the mode of viral infection, latent or lytic. these data indicated that there is no strong correlation between the number of infected cells and the ebv load (ebvl). this can be explained by a highly variable number of ebv copies per infected cell and by lytic replication in some cells. the pl ...201727717030
constitutive activation of t cells by γ2-herpesviral gpcr through the interaction with cellular cxcr4.members of the herpesviral family use multiple strategies to hijack infected host cells and exploit cellular signaling for their pathogenesis and latent infection. among the most intriguing weapons in the arsenal of pathogenic herpesviruses are the constitutively active virally-encoded g protein-coupled receptors (vgpcrs). even though vgpcrs contribute to viral pathogenesis such as immune evasion and proliferative disorders, the molecular details of how vgpcrs continuously activate cellular sign ...201727751885
grey zone lymphoma with features intermediate between diffuse large b-cell lymphoma and classical hodgkin lymphoma: a clinicopathological study of 14 epstein-barr virus-positive cases.to investigate the clinicopathological features of epstein-barr virus (ebv)-positive grey zone lymphoma (gzl) with features intermediate between diffuse large b-cell lymphoma (dlbcl) and classical hodgkin lymphoma (chl).201727735994
mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the lymphoma study association.mediastinal gray zone lymphoma, b-cell lymphomas with intermediate features between classical hodgkin lymphoma and primary mediastinal b-cell lymphoma, have not been well described in the literature. we report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. cases were defined as classical hodgkin lymphoma-like morphology (64.6%) with primary mediastinal b-cel ...201727758822
the impact of ebv and hiv infection on the microenvironmental niche underlying hodgkin lymphoma pathogenesis.the pathogenesis of classical hodgkin lymphoma (chl) is still enigmatic, largely because its tumor cells, the so-called hodgkin and reed-stenberg (hrs) cells, invariably reside in a prominent reactive microenvironment, are rare and therefore difficult to analyze. on the other hand, the broadly investigated chl-derived cell lines are not unequivocally considered as suitable and representative models for this puzzling disease. based on current knowledge, it appears that the cross talk between the ...201727750386
no definite clinical features of immunoglobulin g4-related disease in patients with pulmonary nodular lymphoid hyperplasia.pulmonary nodular lymphoid hyperplasia (pnlh) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin g4 (igg4)-positive plasma cells as in igg4-related disease (igg4-rd). however, it is unclear whether pnlh could be a manifestation of igg4-rd. a recent study reported the presence of epstein-barr virus (ebv) in igg4-related lymphadenopathy. we postulated that a subset of pnlh might represent igg4-related lung disease with ebv-positive lymphocytes as has been reported in igg4-r ...201727720730
ganetespib, an hsp90 inhibitor, kills epstein-barr virus (ebv)-infected b and t cells and reduces the percentage of ebv-infected cells in the blood.hsp90 inhibitors have been shown to kill epstein-barr virus (ebv)-infected cells by reducing the level of ebv ebna-1 and/or lmp1. we treated virus-infected cells with ganetespib, an hsp90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed ebv-positive b and t cells and reduced the level of both ebv ebna-1 and lmp1. treatment of cells with ganetespib also reduced the level of pakt. ganetespib delayed the onset of ebv-positive lymphomas and pr ...201727686857
tax1bp1 downregulation by ebv-mir-bart15-3p enhances chemosensitivity of gastric cancer cells to 5-fu.micrornas (mirnas) are a class of noncoding rna molecules approximately 19 to 25 nucleotides in length that downregulate the expression of target genes at the post-transcriptional level by binding to the 3'-untranslated region (3'-utr). epstein-barr virus (ebv) generates at least 44 mirnas, but the functions of most of these mirnas have not yet been identified. previously, we reported bruce as a target of mir-bart15-3p, a mirna produced by ebv, but our data suggested that there might be other ap ...201727757686
epstein-barr virus associated lymphomas in people with hiv.the present review summarizes the association of the different histotypes of epstein-barr virus (ebv)-associated lymphomas with known genetic lesions and/or oncogenic viruses. a more comprehensive understanding of the complex interplay existing between genetic abnormalities of tumor cells and the viral contribution to the development of ebv-associated lymphomas is pivotal for the development of more effective treatments.201727755151
distinguishing between hepatosplenic t-cell lymphoma and γδ t-cell large granular lymphocytic leukemia: a clinicopathologic, immunophenotypic, and molecular analysis.hepatosplenic t-cell lymphoma (hstcl) is a rare, aggressive t-cell lymphoma that can be challenging to diagnose. in particular, distinguishing hstcl from t-cell large granular lymphocytic (t-lgl) leukemia of γδ t-cell receptor (tcr) type is difficult without examination of a splenectomy specimen. in this study, we systematically assessed a series of hstcl cases for findings reported in the literature as supporting or not supporting the diagnosis of hstcl. we also compared hstcl with a group of c ...201727755009
pd-1-pd-l1 immune-checkpoint blockade in b-cell lymphomas.cancer cells can escape t-cell-mediated cellular cytotoxicity by exploiting the inhibitory programmed cell-death protein 1 (pd-1)/programmed cell death 1 ligand 1 (pd-l1) immune checkpoint. indeed, therapeutic antibodies that block the pd-1-pd-l1 axis induce durable clinical responses against a growing list of solid tumours. b-cell lymphomas also leverage this checkpoint to escape immune recognition, although the outcomes of pd-1-pd-l1 blockade, and the correlations between pd-l1 expression and ...201727805626
clinicopathological characteristics and genomic profile of primary sinonasal tract diffuse large b cell lymphoma (dlbcl) reveals gain at 1q31 and rgs1 encoding protein; high rgs1 immunohistochemical expression associates with poor overall survival in dlbcl not otherwise specified (nos).we aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large b cell lymphoma (dlbcl(sn) ) in a series of 240 cases of dlbcl not otherwise specified [dlbcl(all ()(nos)()) ], including dlbcl(sn) training set (n = 11) and validation set (n = 18), and dlbcl(non-sn) (n = 211).201727775850
cytotoxic epstein-barr virus-positive large b cell lymphoma: a regulatory b cell-derived neoplasia?a new subtype of granzyme b (grb)-producing regulatory b cells (bregs ) has been described recently; these peculiar cytotoxic b cells are increased significantly in interleukin (il)-21-rich settings, and in particular during hiv and epstein-barr virus (ebv) infection. our aim is to report a unique case of an ebv-positive diffuse large b cell lymphoma (dlbcl) with cytotoxic features arisen in an hiv(+) patient, and to understand if this lesion may represent a proliferation of neoplastic cytotoxic ...201727782313
clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in china: a retrospective multicenter study.hemophagocytic lymphohistiocytosis (hlh) is a heterogeneous disease with major diagnostic and therapeutic difficulties. a large-scale multicenter study of pediatric hlh is still lacking in china.201727781387
hodgkin lymphoma, hiv, and epstein-barr virus in malawi: longitudinal results from the kamuzu central hospital lymphoma study.contemporary descriptions of classical hodgkin lymphoma (chl) are lacking from sub-saharan africa where human immunodeficiency virus (hiv) and epstein-barr virus (ebv) are prevalent.201727781380
transient reduction in iga(+) and igg(+) memory b cell numbers in young ebv-seropositive children: the generation r study.the ebv is known to persist in memory b cells, but it remains unclear how this affects cell numbers and humoral immunity. we here studied ebv persistence in memory b cell subsets and consequences on b cell memory in young children. ebv genome loads were quantified in 6 memory b cell subsets in ebv(+) adults. the effects of ebv infection on memory b cell numbers and vaccination responses were studied longitudinally in children within the generation r population cohort between 14 mo and 6 yr of ag ...201727821468
high-throughput protein and mrna expression-based classification of gastric cancers can identify clinically distinct subtypes, concordant with recent molecular classifications.gastric cancers have recently been classified into several types on the basis of molecular characterization, and the new taxonomy has shown to have clinical relevance. however, the technology required for thorough molecular classification is complicated and expensive, currently preventing widespread use. we aimed to reproduce the results of molecular classification using only simple techniques, that is, immunohistochemical analysis and in situ hybridization. we classified a cohort of 349 success ...201727819872
tacrolimus plus sirolimus with or without atg as gvhd prophylaxis in hla-mismatched unrelated donor allogeneic stem cell transplantation.hla-matched related or unrelated donors are not universally available. consequently, patients can be offered hematopoietic stem cell transplantation (hsct) from alternative donors, including mismatched unrelated donors (mmurd), known to cause a higher incidence of acute gvhd (agvhd) and chronic gvhd. in vivo t-cell-depletion strategies, such as antithymocyte globulin (atg) therapy, significantly decrease the risk of gvhd. we performed a multicenter, retrospective study comparing tacrolimus (tac) ...201727819684
epstein-barr virus infection and related hematological diseases.once the epstein-barr virus (ebv) has infected a person, it then latently infects b cells. this latent infection lasts a lifetime. however, ebv can infect t or nk cells (t/nk cells) in rare cases. therefore, ebv causes various hematological diseases. among these diseases, caebv is regarded as the most problematic because, although it is not particularly uncommon, the diagnostic tests for this disease are not covered by health insurance, a serious illness in the "non-active" periods is lacking, a ...201727795539
the long and complicated relationship between epstein-barr virus and epithelial cells.the roles of epithelial cells in infection and persistence of the epstein-barr virus (ebv) have long been difficult to resolve. however, recent developments have reinforced the conclusion that these cells are a major site of virus replication and raised the possibility that, like papillomaviruses, ebv has evolved to take advantage of epithelial differentiation to ensure survival, persistence, and spread.201727795426
high epstein-barr virus load and genomic diversity are associated with generation of gp350-specific neutralizing antibodies following acute infectious mononucleosis.the epstein-barr virus (ebv) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. to better understand the role of ebv-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured ebv gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary ebv infection (acute infectious mononucleosis [aim]) a ...201727733645
epstein-barr virus latent membrane protein 2a (lmp2a) enhances il-10 production through the activation of bruton's tyrosine kinase and stat3.previous data demonstrate that epstein-barr virus latent membrane protein 2a (lmp2a) enhances il-10 to promote the survival of lmp2a-expressing b cell lymphomas. since stat3 is an important regulator of il-10 production, we hypothesized that lmp2a activates a signal transduction cascade that increases stat3 phosphorylation to enhance il-10. using lmp2a-negative and -positive b cell lines, the data indicate that lmp2a requires the early signaling molecules of the syk/ras/pi3k pathway to increase ...201727792904
association of epstein-barr virus reactivation with the recovery of cd4/cd8 double-negative t lymphocytes after haploidentical hematopoietic stem cell transplantation.ebv infection is one of the life-threatening clinical complications in patients who underwent haploidentical hematopoietic stem cell transplantation (haplohsct). although immune recovery is recognized to be crucial for decreasing subsequent morbidity of infections, the link between t-cell recovery and ebv infection after haplohsct remains elusive. we recently compared the influences of different doses of antithymocyte globulin conditioning on the t-cell reconstitution post haplohsct and suggeste ...201727797369
regulation of the viral life cycle by murine gammaherpesvirus 68 micrornas.γ-herpesviruses (γhv) such as epstein-barr virus and kaposi's sarcoma-associated herpesvirus are important human pathogens involved in lymphoproliferation and tumorigenesis. murine gammaherpesvirus 68 (mhv-68, γhv-68) is an effective model for the study of γhv pathogenesis and host-virus interaction because it is closely related to human γhv. similarly to human γhv, mhv-68 encodes 15 micrornas (mirnas). although their functions remain unknown, they are thought to regulate the viral life cycle or ...201727837274
achievement of disease control with donor-derived eb virus-specific cytotoxic t cells after allogeneic peripheral blood stem cell transplantation for aggressive nk-cell leukemia.aggressive nk-cell leukemia (ankl) is characterized by systemic infiltration of epstein-barr virus (ebv)-associated natural killer cells and poor prognosis. we report a case of ankl in which ebv-specific cytotoxic t lymphocytes (ctls) were induced. a 41-year-old male suffered from fever, pancytopenia, and hepatosplenomegaly. the number of abnormal large granular lymphocytes in the bone marrow was increased and the cells were positive for cd56 and ebv-encoded small nuclear rnas. the patient was d ...201727830541
hydroa vacciniforme-like skin lesions in epstein-barr-virus-associated t-cell lymphoproliferation with subsequent development of aggressive nk/t-cell lymphoma.is missing (short communication).201727826612
epstein-barr virus infection and gene promoter hypermethylation in rheumatoid arthritis patients with methotrexate-associated b cell lymphoproliferative disorders.we analyzed cpg-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (ra) patients with methotrexate (mtx)-associated large b cell lymphoproliferative disorder (blpd), 11 ra patients with non-mtx-associated blpd (non-mtx-blpd), 22 controls with diffuse large b cell lymphoma (dlbcl), and 10 controls with epstein-barr virus (ebv)(+) dlbcl. among them, tumor cells from ebv(+) mtx-blpd patients and control ebv(+) dlbcl patients had significantly lower ...201727864689
the linear ubiquitin assembly complex modulates latent membrane protein 1 activation of nf-κb and interferon regulatory factor 7.recently, linear ubiquitin assembly complex (lubac)-mediated linear ubiquitination has come into focus due to its emerging role in activation of nf-κb in different biological contexts. however, the role of lubac in lmp1 signaling leading to nf-κb and interferon regulatory factor 7 (irf7) activation has not been investigated. we show here that rnf31, the key component of lubac, interacts with lmp1 and irf7 in epstein-barr virus (ebv)-transformed cells and that lubac stimulates linear ubiquitinati ...201727903798
a human fab exclusively binding to the extracellular domain of lmp2a.in the areas of north africa, southeast asia as well as south china, nasopharyngeal carcinoma (npc) is among the most widespread cancers. plenty of research findings confirmed that epstein-barr virus (ebv) played a crucial role in npc. ebv-encoded latent membrane protein 2a (lmp2a) which continuously expressed in cell membrane protein induced an epithelial-mesenchymal transition and increased the number of side population stem-like cancer cells in npc. this reveals that lmp2a could contribute to ...201727845040
the epstein-barr virus ebna2 protein induces a subset of notch target genes in thyroid cancer cell lines but fails to suppress proliferation.epstein-barr virus is associated with lymphoid and epithelial malignancies and has been reported to infect thyroid cells. the epstein-barr virus protein, ebna2, regulates viral and cellular promoters by binding to rbp-jκ. similarly, notch1, a tumor suppressor protein in thyroid epithelial cells, competes with ebna2 for binding to overlapping sites on rbp-jκ. ebna2 activates a subset of notch-responsive genes in lymphocytes and myocytes; however, the effect of ebna2 expression on notch targets in ...201727847111
successful cord blood stem cell transplantation for an adult case of chronic active epstein-barr virus infection.a 41-year-old man was referred to our hospital for treatment of anaplastic lymphoma kinase (alk)-negative anaplastic large cell lymphoma. chronic active epstein-barr virus (caebv) was diagnosed based on the findings of elevated ebv antibody titers and positive ebv-dna in the peripheral blood, and cord blood stem cell transplantation (cbt) was performed. the ebv-dna levels in the blood fell below the limit of detection. his lymphoma relapsed on day 165 with the appearance of eruptions, which disa ...201727904117
nivolumab in the treatment of hodgkin lymphoma.despite an extensive immune infiltrate that is recruited to the tumor by malignant reed-sternberg cells in hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. the ineffective immune response is in part due to pd-1 signaling that renders intratumoral immune cells anergic. reed-sternberg cells have been shown to upregulate expression of the pd-1 ligands, pd-l1 and pd-l2, due to either genetic alterations at chromosome 9p24.1 or epstein-barr v ...201727881581
management of post-transplant lymphoproliferative disorders.post-transplant lymphoproliferative disease (ptld) is a major complication of hematopoietic stem cell and solid organ transplantation. the incidence of transplantation in childhood has been steadily rising, making ptld the most common form of lymphoproliferation in childhood. the purpose of this review is to summarize the role of the epstein-barr virus (ebv) in the pathophysiology and discuss the management of ptld.201727906865
hla-mismatched haploidentical transplantation using low-dose anti-thymocyte globulin (atg: thymoglobulin).to clarify optimal strategies for human leukocyte antigen (hla)-mismatched haploidentical hematopoietic stem cell transplantation (hsct).201727905258
isolation and characterization of exosomes released by ebv-immortalized cells.epstein-barr virus is an oncogenic herpesvirus associated with several human malignancies. although the details of the molecular steps involved in ebv-mediated cell transformation and immune evasion are not fully known, a number of viral products, including ebv latent proteins and non-protein coding rnas have been shown to be involved, directly or indirectly in these processes. in recent years, a growing body of data indicates that some viruses are able to transport selected products to neighbor ...201727873273
analysis of ebv transcription using high-throughput rna sequencing.high-throughput sequencing of rna is used to analyze the transcriptomes of viruses and cells, providing information about transcript structure and abundance. a wide array of programs and pipelines has been created to manage and interpret the abundance of data generated from high-throughput rna sequencing experiments. this protocol details the use of free and open-source programs to align rna-seq reads to a reference genome, visualize read coverage and splice junctions, estimate transcript abunda ...201727873270
affinity purification-mass spectroscopy methods for identifying epstein-barr virus-host interactions.considerable insight into the function and mechanism of action of viral proteins has come from identifying the cellular proteins with which they interact. in recent years, mass spectrometry-based methods have emerged as the method of choice for protein interaction discovery due to their comprehensive and unbiased nature. methods involving single affinity purifications of epitope-tagged viral proteins (ap-ms) and tandem affinity purifications of viral proteins with two purification tags (tap tagg ...201727873268
generation and infection of organotypic cultures with epstein-barr virus.while numerous model systems are available to study ebv latency in b cells and have contributed greatly to our understanding of the role of these cells in the viral life cycle, models to study the ebv life cycle in epithelial cells in vitro are lacking. epithelial cells are poorly infected in vitro, and ebv-infected cell lines have not been successfully obtained from epithelial tumors. recently, we have demonstrated that organotypic cultures of oral keratinocytes can be used as a model to study ...201727873267
epstein-barr virus: clinical diagnostics.the vast majority of the human adult population is infected with epstein-barr virus (ebv), and the majority of the ebv-infected individuals tolerates the infection well, without any further symptoms after primary infection. in cases of individuals which undergo primary infection in the form of an infectious mononucleosis, or which have undergone primary infection in their past, it is sometimes important to appraise symptomatic disease or differentiate infectious mononucleosis from other conditio ...201727873265
current trends and alternative scenarios in ebv research.epstein-barr virus (ebv) infection is associated with several distinct hematological and epithelial malignancies, e.g., burkitt lymphoma, hodgkin lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and others. the association with several malignant tumors of local and worldwide distribution makes ebv one of the most important tumor viruses. furthermore, because ebv can cause posttransplant lymphoproliferative disease, transplant medicine has to deal with ebv as a major pathogenic virus second ...201727873264
incidental ebv-positivity in paediatric post-transplant specimens demonstrates the need for stringent criteria for diagnosing post-transplant lymphoproliferative disorders.to examine the need for minimal diagnostic criteria for post-transplant lymphoproliferative disorders (ptld) in children, we sought to determine the rate of incidental epstein-barr virus (ebv)-positivity in tissues from organ transplant recipients (otr).201727852687
ebv-directed t cell therapeutics for ebv-associated lymphomas.epstein barr virus (ebv) is a human gamma herpes virus that establishes latency in b cells after primary infection. ebv generally only causes a mild, self-limiting viral illness but is also associated with several malignancies including posttransplantation lymphoproliferative disorder in the immunosuppressed host as well as hodgkin and non-hodgkin lymphoma in the immune competent host. the expression of ebv antigens by lymphoma has important applications as targets for adoptive t cell therapy. h ...201727873282
generation and analysis of humanized mouse model of ebv infection.the recent development of severely immunodeficient mouse strains enabled the production of new-generation humanized mice, in which major components of the human immune system are reconstituted. these new-generation humanized mice can be infected with human pathogenic viruses that do not infect regular mice and target cells of the hematoimmune system. here we describe the method for preparing humanized mice, infecting them with ebv, and for their virological and immunological analyses. the result ...201727873281
mice with reconstituted human immune system components as a tool to study immune cell interactions in ebv infection.recent developments in mouse models that harbor part of a human immune system have proved extremely valuable to study the in vivo immune response to human specific pathogens such as epstein-barr virus. over the last decades, advances in immunodeficient mouse strains that can be used as recipients for human immune cells have greatly enhanced the use of these models. here, we describe the generation of mice with reconstituted human immune system (his mice) using immunocompromised mice transplanted ...201727873280
characterization of ebv promoters and coding regions by sequencing pcr-amplified dna fragments.dna sequencing approaches originally developed in two directions, the chemical degradation method and the chain-termination method. the latter one became more widespread and a huge amount of sequencing data including whole genome sequences accumulated, based on the use of capillary sequencer systems and the application of a modified chain-termination method which proved to be relatively easy, fast, and reliable. in addition, relatively long, up to 1000 bp sequences could be obtained with a singl ...201727873276
terminal repeat analysis of ebv genomes.epstein-barr virus (ebv) was the first human virus associated directly with human malignancies. during ebv infection of various host cells the double-stranded linear ebv dna carried by the virions undergoes circularization. since there are variable numbers of terminal repetitions (trs) at the ends of the linear ebv genome, the resulting circular episomes enclose a variable number of trs. thus, in cells carrying viral episomes, the sizes of the terminal restriction enzyme fragments of ebv is affe ...201727873275
clinically mild encephalitis/encephalopathy with a reversible splenial lesion accompanied by epstein-barr virus hemophagocytic lymphohistiocytosis: a case report and review of the literature.central nervous system involvement in hemophagocytic lymphohistiocytosis (hlh) is associated with a poor outcome. for such patients, it is unknown whether more aggressive therapies, such as intrathecal methotrexate or hydrocortisone, are inevitably required. we present a very rare case of 3-year-old japanese girl who developed mild encephalitis/encephalopathy with a reversible splenial lesion, accompanied by epstein-barr virus-associated hlh, and review previous similar reports. our case and pre ...201727879539
cerebrospinal fluid anti-epstein-barr virus specific oligoclonal igm and igg bands in patients with clinically isolated and guillain-barré syndrome.epstein-barr virus (ebv) has been implicated in multiple sclerosis (ms) pathogenesis. we aimed to assess the frequency of ebv-specific igg and igm oligoclonal bands (ocb) in cerebrospinal fluid (csf) of 50 patients with clinically isolated syndrome (cis) and in 27 controls with guillain-barré syndrome (gbs). furthermore, we assessed correlations between the presence of ocb and cis patients' csf, mri, and clinical variables. there was no difference in the proportion of cis and gb patients with po ...201727878471
resolution of multifocal epstein-barr virus-related smooth muscle tumor in a patient with gata2 deficiency following hematopoietic stem cell transplantation.we performed allogeneic hematopoietic stem cell transplantation in a patient with gata2 deficiency and an epstein-barr virus (ebv)-related spindle cell tumor involving the liver and possibly bone. he received a matched-related donor transplant with donor peripheral blood stem cells following a myeloablative conditioning regimen. he achieved rapid and high levels of donor engraftment and had complete reversal of the clinical and immunologic phenotype of monomac/gata2 deficiency and eradication of ...201727924436
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