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crispr/cas9-mediated genome editing in epstein-barr virus-transformed lymphoblastoid b-cell lines.epstein-barr virus (ebv) efficiently transforms primary human b cells into immortalized lymphoblastoid cell lines (lcls), which are extensively used in human genetic, immunological and virological studies. lcls provide unlimited sources of dna for genetic investigation, but can be difficult to manipulate, for instance because low retroviral or lentiviral transduction frequencies hinder experiments that require co-expression of multiple components. this unit details clustered regularly interspace ...201829337376
modulating gene expression in epstein-barr virus (ebv)-positive b cell lines with crispra and crispri.epstein-barr virus (ebv) transforms small resting primary b cells into large lymphoblastoid cells which are able to grow and survive in vitro indefinitely. these cells represent a model for oncogenesis. in this unit, variants of conventional clustered regularly interspaced short palindromic repeats (crispr), namely the crispr activation (crispra) and crispr interference (crispri) methods, are discussed in the context of gene regulation at genomic dna promoter and enhancer elements. lymphoblastoi ...201829337370
epstein barr virus and invasive mammary carcinomas: ebna, ebers and molecular profile in a population of west algeria.breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. a possible viral etiology for breast cancer has been proposed and epstein-barr virus (ebv) is a widely studied candidate virus. the objective of this study is to determine the association of ebv infection with infiltrating ductal carcinomas (idc). this descriptive study was carried out in the laboratory of developmental biology and differentiation ...201829336321
toll-like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?pathogen infections and dysregulated toll-like receptor (tlr)-mediated innate immune responses are suspected to play key roles in autoimmunity. among tlrs, tlr7 and tlr9 have been implicated in several autoimmune conditions, mainly because of their ability to promote abnormal b cell activation and survival. recently, we provided evidence of epstein-barr virus (ebv) persistence and reactivation in the thymus of myasthenia gravis (mg) patients, suggesting an involvement of ebv in the intrathymic p ...201829363775
no increased risk of posttransplant lymphoproliferative disorder following alemtuzumab induction in kidney transplant.posttransplant lymphoproliferative disorder is a known complication of solid-organ transplant. the use of depleting induction agents has demonstrated varying associations with incidence of posttransplant lymphoproliferative disorder. alemtuzumab, a depleting induction agent for kidney transplant patients, has shown promising results in reducing the risk of acute rejection and graft loss in the first year. its unique mechanism of depleting both t-cell and b-cell populations may be beneficial in p ...201829363415
expression of activating nk-cell receptors is a hallmark of the innate-like t-cell neoplasm in peripheral t-cell lymphomas.peripheral t- or nk-cell lymphomas are rare and difficult-to-recognize diseases. it remains arduous to distinguish between nk cell- and cytotoxic t lymphocyte-derived lymphomas through routine histologic evaluation. to clarify the cells of origin, we focused on nk-cell receptors and examined the expression using immunohistochemistry in 22 cases with t- and nk-cell neoplasms comprising of angioimmunoblastic t-cell lymphoma, alk-positive and -negative anaplastic large cell lymphomas, extranodal nk ...201829363227
herpesvirus deconjugases inhibit the ifn response by promoting trim25 autoubiquitination and functional inactivation of the rig-i signalosome.the n-terminal domains of the herpesvirus large tegument proteins encode a conserved cysteine protease with ubiquitin- and nedd8-specific deconjugase activity. the proteins are expressed during the productive virus cycle and are incorporated into infectious virus particles, being delivered to the target cells upon primary infection. members of this viral enzyme family were shown to regulate different aspects of the virus life cycle and the innate anti-viral response. however, only few substrates ...201829357390
interferon regulatory factor 8 regulates aspase-1 expression to facilitate epstein-barr virus reactivation in response to b cell receptor stimulation and chemical induction.interferon regulatory factor 8 (irf8), also known as interferon consensus sequence-binding protein (icsbp), is a transcription factor of the irf family. irf8 plays a key role in normal b cell differentiation, a cellular process that is intrinsically associated with epstein-barr virus (ebv) reactivation. however, whether irf8 regulates ebv lytic replication remains unknown. in this study, we utilized a crispr/cas9 genomic editing approach to deplete irf8 and found that irf8 depletion dramatically ...201829357389
association of cytomegalovirus and epstein-barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study.earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. few studies have investigated the association of cytomegalovirus and epstein-barr virus with cognitive decline longitudinally. our aim was to examine whether cytomegalovirus and epstein-barr virus are associated with cognitive decline in adults method: the study sample is from the finnish health 2000 survey (brif8901, n = 7112), which is representative of the finni ...201829355820
characterization of skin blister fluids from children with epstein-barr virus-associated lymphoproliferative disease.epstein-barr virus (ebv)-associated t- or natural killer (nk)-cell lymphoproliferative disease (lpd) is a heterogeneous group of disorders characterized by chronic proliferation of ebv-infected lymphocytes. patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (hmb) and hydroa vacciniforme (hv)-like eruption, which are characterized by blister formation and necrotic ulceration. skin biopsy specimens show inflammatory reactions comprising ebv-infected ...201829352500
current perspectives on erythema multiforme.recognition and timely adequate treatment of erythema multiforme remain a major challenge. in this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. the diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histologic ...201829352387
epstein-barr virus encoded latent membrane protein 1 suppresses necroptosis through targeting ripk1/3 ubiquitination.necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (ripk1) and ripk3. this form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. however, only a few viral species such as herpes simplex virus (hsv) and cytomegalovirus (cmv) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, ...201829352166
membranoproliferative glomerulonephritis and interstitial nephritis in the setting of epstein-barr virus-related hemophagocytic syndrome
.hemophagocytic syndrome (hps) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. less frequently, glomerulopathy can also be found.201829350173
interferon regulatory factor 5 is a potential target of autoimmune response triggered by epstein-barr virus and mycobacterium avium subsp. paratuberculosis in rheumatoid arthritis: investigating a mechanism of molecular mimicry.rheumatoid arthritis (ra) is a chronic disease characterised by a pro-inflammatory cytokines linked erosive joint damage and by humoral and cellular response against a broad range of self-peptides. molecular mimicry between epstein-barr virus (ebv), mycobacterium avium subsp. paratuberculosis (map) and host peptides has long been regarded as an ra pathogenetic mechanism. using bioinformatic analysis we identified high sequence homology among interferon regulatory factor 5 (irf5), ebv antigen bol ...201829352853
the potential of currently unavailable herpes virus vaccines.despite overwhelming experimental work, there are no licensed vaccines against the most frequent alphaherpesviruses, namely herpes simplex virus 1 and 2 (hsv1 and 2) nor against the epstein-barr virus (ebv), a member of the subfamily gammaherpesvirus. areas covered: since the dnas of both hsvs reside in the regional sensory ganglia in a latent state (i.e. as circularized episomal molecules), a corresponding vaccine might be useful for immunotherapy rather than prevention of primary infection. he ...201829313728
are infectious agents involved in the pathogenesis of postpartum psychosis?since postpartum psychosis has been linked to activation of the immune system, it has been hypothesized that infectious agents may be involved in the pathogenesis of this disorder. we therefore investigated whether exposure to pathogens that can infect the central nervous system is increased in patients with postpartum psychosis.201829310062
viral unmasking of cellular 5s rrna pseudogene transcripts induces rig-i-mediated immunity.the sensor rig-i detects double-stranded rna derived from rna viruses. although rig-i is also known to have a role in the antiviral response to dna viruses, physiological rna species recognized by rig-i during infection with a dna virus are largely unknown. using next-generation rna sequencing (rnaseq), we found that host-derived rnas, most prominently 5s ribosomal rna pseudogene 141 (rna5sp141), bound to rig-i during infection with herpes simplex virus 1 (hsv-1). infection with hsv-1 induced re ...201829180807
human mhc-ii with shared epitope motifs are optimal epstein-barr virus glycoprotein 42 ligands-relation to rheumatoid arthritis.rheumatoid arthritis (ra) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. although the pathogenesis of ra remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. especially genetic factors play a vital role in the onset of disease, as the heritability of ra is 50-60%, with the human leukocyte antigen (hla) alleles accounting for at least 3 ...201829361739
kinetics of double-stranded dna viremia after allogeneic hematopoietic cell transplantation.improved understanding of double-stranded dna (dsdna) virus kinetics after hematopoietic cell transplantation (hct) would facilitate development of therapeutic strategies.201829020348
torquetenovirus dynamics and immune marker properties in patients following allogeneic hematopoietic stem cell transplantation: a prospective longitudinal study.torquetenovirus (ttv) has been proposed as a marker of immune function in patients receiving immunosuppression after solid organ transplantation. this study aimed to define ttv plasma dynamics and investigate clinical associations in patients following allogeneic hematopoietic stem cell transplantation (hsct). this was a single-center prospective longitudinal study involving 50 consecutive patients treated with hsct between march 2015 and april 2016. ttv plasma dna levels were measured with quan ...201829032273
new-onset diabetes after kidney transplantation: can the risk be modified by choosing immunosuppression regimen based on pretransplant viral serology?this study aimed to analyze adult kidney transplant recipients (ktrs) for the risk of new-onset diabetes after transplantation (nodat) associated with viral serologies and immunosuppression regimens [tacrolimus (tac) + mycophenolate (mpa), cyclosporine (csa) + mpa, sirolimus (srl) + mpa, srl + csa or srl +tac].201829045704
malaria, epstein-barr virus, vitamin a and burkitt's lymphoma: response to joob and wiwanitkit. 201829055028
malaria, epstein-barr virus, vitamin a and burkitt's lymphoma. 201829055026
complete response of age-related epstein-barr virus-associated polymorphic nodal lymphoproliferative disease of plasmacytic type to low-dose lenalidomide. 201829063179
epstein-barr virus positive diffuse large b cell lymphoma with g17v rhoa mutation arising from peripheral t cell lymphoma, not otherwise specified. 201829063178
an anergic immune signature in the tumor microenvironment of classical hodgkin lymphoma is associated with inferior outcome.the classical hodgkin lymphoma (chl) tumor microenvironment shows an ongoing inflammatory response consisting of varying degrees of infiltrating eosinophils, mast cells, macrophages, regulatory t lymphocytes (tregs), and activated lymphocytes surrounding the malignant cells. herein, different immune signatures are characterized and correlated with treatment outcome.201829064587
human papillomavirus and world health organization type iii nasopharyngeal carcinoma: multicenter study from an endemic area in southern china.the current study was conducted to study the incidence of human papillomavirus (hpv)-associated nasopharyngeal carcinoma (npc) in southern china and the corresponding treatment outcome.201829072774
epstein-barr virus positive diffuse large b-cell lymphoma presenting with vaginal sloughing and ulcerated skin nodule.malignant lymphomas presenting in the female genital tract are extremely rare. we report a case of epstein-barr virus associated diffuse large b-cell lymphoma of the genital tract and skin in a 60-year-old woman on long-term azathioprine.201829086996
toll-like receptor 9 polymorphism is associated with increased epstein-barr virus and cytomegalovirus acquisition in hiv-exposed infants.: polymorphisms in the toll-like receptor 9 1635 locus have been associated with hiv-1 acquisition and progression. cytomegalovirus (cmv) and epstein-barr virus (ebv) acquisition were compared between kenyan hiv-exposed infants by 1635 genotype. having one or more copies of the 1635a allele was associated with increased cmv acquisition in hiv-infected infants (42 vs. 11%, p = 0.03) and increased risk of ebv acquisition in hiv-exposed uninfected infants (hazard ratio = 4.2, p = 0.02) compared wit ...201829112074
b lymphoblastic leukemia/lymphoma with burkitt-like morphology and igh/myc rearrangement: report of 3 cases in adult patients.isolated myc rearrangement without other recurrent genetic abnormalities is rare in b lymphoblastic leukemia/lymphoma (b-all/lbl), with most cases reported in pediatric patients. we report 3 adult cases with lymphoblasts showing a precursor b cell immunophenotype, and isolated myc/igh translocation. all 3 cases occurred in male patients with initial presentation of diffuse lymphadenopathy. cases 1 and 2 had b-all with significantly increased lymphoblasts in peripheral blood and bone marrow. case ...201829112016
cancer therapy-associated lymphoproliferative disorders: an under-recognized type of immunodeficiency-associated lymphoproliferative disorder.we describe the clinicopathologic features of 17 patients who had a hematologic malignancy of various types, were treated, and subsequently developed a lymphoproliferative disorder (lpd). there were 10 men and 7 women with a median age of 59 years (range, 36 to 83 y). the primary hematologic neoplasms included: 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, 3 plasma cell myeloma, 2 acute monoblastic leukemia, and 1 case each of mixed-phenotype acute leukemia, chronic myeloid leukemia ...201829112013
analysis of epstein-barr virus genomes and expression profiles in gastric adenocarcinoma.epstein-barr virus (ebv) is a causative agent of a variety of lymphomas, nasopharyngeal carcinoma (npc), and ∼9% of gastric carcinomas (gcs). an important question is whether particular ebv variants are more oncogenic than others, but conclusions are currently hampered by the lack of sequenced ebv genomes. here, we contribute to this question by mining whole-genome sequences of 201 gcs to identify 13 ebv-positive gcs and by assembling 13 new ebv genome sequences, almost doubling the number of av ...201829093097
early epstein-barr virus genomic diversity and convergence toward the b95.8 genome in primary infection.over 90% of the world's population is persistently infected with epstein-barr virus. while ebv does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (aim) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. at present, very few primary, circulating ebv genomes have been sequenced directly from infected individuals. while low levels of diversity and low viral evolution rates have been pr ...201829093087
serologic and viral genome prevalence of hsv, ebv, and hcmv among healthy adults in wuhan, china.the worldwide infection rate of herpesvirus is high, but the detailed prevalence in china, especially the central area, remains unclear. in the present study, the prevalence of herpes simplex virus (hsv), epstein-barr virus (ebv), and human cytomegalovirus (hcmv) was investigated in 303 healthy adults in wuhan, a representative city in central china. viral-specific igg and igm titers were examined in the serum by chemiluminescent immunoassay, and the existence of viral genomic dna in blood cells ...201829091300
risk factors for post-transplant lymphoproliferative disorder after thymoglobulin-conditioned hematopoietic cell transplantation.epstein-barr virus (ebv)-induced post-transplant lymphoproliferative disorder (ptld) occurs frequently when rabbit antithymocyte globulin (atg) is used in hematopoietic cell transplant (hct) conditioning. we retrospectively studied 554 patients undergoing atg-conditioned myeloablative hct. strategies used to minimize mortality due to ptld were either therapy of biopsy-diagnosed ptld in the absence of ebv dnaemia monitoring (n = 266) or prompt therapy of presumed ptld (based on clinical/radiologi ...201829114932
c-myc represses transcription of epstein-barr virus latent membrane protein 1 early after primary b cell infection.recent evidence has shown that the epstein-barr virus (ebv) oncogene lmp1 is not expressed at high levels early after ebv infection of primary b cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (lcls). in this study, we found that expression of lmp1 increased 50-fold between 7 days postinfection and the lcl state. metabolic labeling of nascent transcribed mrna indicated that this was primarily a transcription-mediated event. ebna2, the key ...201829118124
epstein-barr virus protein eb2 stimulates translation initiation of mrnas through direct interactions with both poly(a)-binding protein and eukaryotic initiation factor 4g.epstein-barr virus (ebv) expresses several mrnas produced from intronless genes that could potentially be unfavorably translated compared to cellular spliced mrnas. to overcome this situation, the virus encodes an rna-binding protein (rbp) called eb2, which was previously found to both facilitate the export of nuclear mrnas and increase their translational yield. here, we show that eb2 binds both nuclear and cytoplasmic cap-binding complexes (cbc and eukaryotic initiation factor 4f [eif4f], resp ...201829142127
target-induced proximity ligation triggers recombinase polymerase amplification and transcription-mediated amplification to detect tumor-derived exosomes in nasopharyngeal carcinoma with high sensitivity.tumor-derived exosomes (texs) are extracellular vesicles that are continuously released into the blood by tumor cells and carry specific surface markers of the original tumor cells. substantial evidence has implicated texs as attractive diagnostic markers for cancer. however, the detection of texs in blood at an early tumor stage is challenging due to their very low concentration. here, we established a method called pla-rpa-tma assay that allows texs to be detected with high sensitivity and spe ...201829145073
metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas.currently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed pcrs. with metagenomic deep sequencing (mds), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid.201829122821
genetic predictors of response to systemic therapy in esophagogastric cancer.the incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. chemotherapy as well as anti-her2 and pd-1 antibodies are standard treatments. to identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. there was no association between homologous recombination deficiency defects and response to platinum-b ...201829122777
programmed death-1 ligands pd-l1 and pd-l2 show distinctive and restricted patterns of expression in lymphoma subtypes.the success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. because efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (pd-1) ligands, we evaluated the expression of pd-l1 and pd-l2 proteins using immunohistochemistry in more than 702 diagnostic lymphoma biopsies. in classical h ...201829122656
the alice-in-wonderland syndrome.in 1955, english psychiatrist john todd defined the alice-in-wonderland syndrome (aiws) as self-experienced paroxysmal body-image illusions involving distortions of the size, mass, or shape of the patient's own body or its position in space, often accompanied by depersonalization and/or derealization. aiws had been described by american neurologist caro lippman in 1952, but todd's report was the most influential. todd named the syndrome for the perceptual disorder of altered body image experienc ...201829151098
potential cancer chemopreventive and anticancer constituents from the fruits of ficus hispida l.f. (moraceae).ficus hispida l.f. (moraceae) has been used as alternative for traditional medicine in the treatment of various ailments including cancer-cure. the aim of this study was to evaluate the cancer chemopreventive and anticancer activities of crude extracts of f. hispida, with the objective to screen the inhibition of epstein-barr virus early antigen, and cytotoxic active components, and provide foundation for potential applications of this promising medical plant.201829197545
viral dnaemia and immune suppression in pediatric sepsis.demonstrate that dna viremia is common in pediatric sepsis and quantitate its associations with host immune function and secondary infection risk.201829189638
conformational dynamics and free energy of bhrf1 binding to bim bh3.the interaction between the bim bh3 peptide and the viral protein bhrf1 is pivotal to understanding the fundamental molecular details of the mechanism used by the epstein-barr virus to trick the mammalian immune system. here, we study the mechanism of binding/unbinding and compute the free energy for the association of the bim peptide to the bhrf1 protein. key elements of the binding mechanism are the conformational rearrangement together with a main free energy barrier of 11.5kcal/mol. the simu ...201829153883
reply to genomic profiles of nasopharyngeal carcinoma: the importance of histological subtyping and epstein-barr virus in situ assays. 201829165787
genomic profiles of nasopharyngeal carcinoma: the importance of histological subtyping and epstein-barr virus in situ assays. 201829165785
what is that rash?a healthy 15-month-old girl presented to the emergency department with a 24-hour history of fever and rash. the initial blanching rash developed into non-blanching areas with associated leg swelling. she had received no recent medications, had no known drug allergies and no unwell contacts.on examination, she was feverish at 38.6°c, capillary refill time was <2 s with warm peripheries, heart rate 169 bpm and blood pressure 94/59 mm hg. a palpable purpuric rash was evident on all four limbs and f ...201827799151
coordinated repression of bim and puma by epstein-barr virus latent genes maintains the survival of burkitt lymphoma cells.while the association of epstein-barr virus (ebv) with burkitt lymphoma (bl) has long been recognised, the precise role of the virus in bl pathogenesis is not fully resolved. ebv can be lost spontaneously from some bl cell lines, and these ebv-loss lymphoma cells reportedly have a survival disadvantage. here we have generated an extensive panel of ebv-loss clones from multiple bl backgrounds and examined their phenotype comparing them to their isogenic ebv-positive counterparts. we report that, ...201828960205
oncogenic spiral by infectious pathogens: cooperation of multiple factors in cancer development.chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral fac ...201829143406
the oncogenic role of epstein-barr virus-encoded micrornas in epstein-barr virus-associated gastric carcinoma.epstein-barr virus (ebv) infection is detected in various epithelial malignancies, such as nasopharyngeal carcinoma (npc) and gastric cancer (gc). ebv comprises some unique molecular features and encodes viral genes and micrornas (mirnas) by its own dna sequence. ebv genes are required to maintain latency and contribute to oncogenic property. mirnas encoded by ebv have been shown to contribute to initiation and progression of ebv-related malignancies. by a number of genomic profiling studies, so ...201828990284
diagnostic value of the epstein-barr virus serological markers in patients with nasopharyngeal carcinoma in cases of undetectable primary tumor location.the goal of this work was to describe a method for diagnosis of the non-keratinizing nasopharyngeal carcinoma (nnpc) in cases of the undetectable primary tumor location. the method is based on evaluation of igg and iga antibody levels to the capsid (vca) and early antigens (ea) of the epstein-barr virus (ebv). the diagnosis of nnpc is established by a so-called decision rule. the latter was created by mathematical processing of the method of multifactor analysis of the results of anti-ebv antibo ...201829323852
a conserved eph family receptor-binding motif on the gh/gl complex of kaposi's sarcoma-associated herpesvirus and rhesus monkey rhadinovirus.kaposi's sarcoma-associated herpesvirus (kshv) is a human oncogenic virus associated with kaposi's sarcoma and two b-cell malignancies. the rhesus monkey rhadinovirus (rrv) is a virus of nonhuman primates that is closely related to kshv. eph family receptor tyrosine kinases (ephs) are cellular receptors for the gh/gl glycoprotein complexes of both kshv and rrv. through sequence analysis and mutational screens, we identified conserved residues in the n-terminal domain of kshv and rrv glycoprotein ...201829432452
experimental co-transmission of simian immunodeficiency virus (siv) and the macaque homologs of the kaposi sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv).macaque rfhv and lcv are close homologs of human kshv and ebv, respectively. no experimental model of rfhv has been developed due to the lack of a source of culturable infectious virus. screening of macaques at the washington national primate research center detected rfhv in saliva of siv-infected macaques from previous vaccine studies. a pilot experimental infection of two naïve juvenile pig-tailed macaques was initiated by inoculation of saliva from siv-infected pig-tailed and cynomolgus macaq ...201830444879
optimization of a high-cell-density polyethylenimine transfection method for rapid protein production in cho-ebna1 cells.for pre-clinical evaluation of biotherapeutic candidates, protein production by transient gene expression (tge) in chinese hamster ovary (cho) cells offers important advantages, including the capability of rapidly and cost-effectively generating recombinant proteins that are highly similar to those produced in stable cho clones. we have established a novel cho clone (cho-3e7) expressing a form of the epstein-barr virus nuclear antigen-1 (ebna-1) with improved tge productivity relative to parenta ...201829886030
co-amplification of ebna-1 and pylt through dhfr-mediated gene amplification for improving foreign protein production in transient gene expression in cho cells.despite the relatively low transfection efficiency and low specific foreign protein productivity (qp) of chinese hamster ovary (cho) cell-based transient gene expression (tge) systems, tge-based recombinant protein production technology predominantly employs cho cells for pre-clinical research and development purposes. to improve tge in cho cells, epstein-barr virus nuclear antigen-1 (ebna-1)/polyoma virus large t antigen (pylt)-co-amplified recombinant cho (rcho) cells stably expressing ebna-1 ...201829654557
viral etiology of sporadic cases of parotitis among children in korea during 2013-2014.recent years have seen a high incidence of mumps, which is generally diagnosed based on clinical features, especially parotitis, without laboratory confirmation in korea. to better understand the epidemiology of mumps in korean children, we investigated sporadic suspected mumps cases with parotitis. in total, 237 buccal swabs or throat swabs collected from children with parotitis who had been clinically diagnosed with mumps were tested using real-time pcr for the detection of six viruses (epstei ...201828876460
the interaction between mitochondria and oncoviruses.mitochondria play important roles in multiple aspects of viral tumorigenesis. mitochondrial genomes contribute to the host's genetic background. after viruses enter the cell, they modulate mitochondrial function and thus alter bioenergetics and retrograde signaling pathways. at the same time, mitochondria also regulate and mediate viral oncogenesis. in this context, oncogenesis by oncoviruses like hepatitis b virus (hbv), hepatitis c virus (hcv), human papilloma virus (hpv), human immunodeficien ...201828962899
effects of deoxynivalenol- and zearalenone-contaminated feed on the gene expression profiles in the kidneys of piglets.fusarium mycotoxins deoxynivalenol (don) and zearalenone (zen), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. consequently, the main objective of this study was to elucidate don and zen effects on the mrna expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets.201828920417
herpes virus reactivation in astronauts during spaceflight and its application on earth.latent herpes virus reactivation has been demonstrated in astronauts during shuttle (10-16 days) and international space station (≥180 days) flights. following reactivation, viruses are shed in the body fluids of astronauts. typically, shedding of viral dna is asymptomatic in astronauts regardless of mission duration; however, in some cases, live/infectious virus was recovered by tissue culture that was associated with atopic-dermatitis or skin lesions during and after spaceflight. hypothalamic- ...201930792698
t-cell/histiocyte-rich large b-cell lymphoma of the larynx in a juvenile japanese macaque (macaca fuscata).an 11-month-old female japanese macaque (macaca fuscata), born in captivity in a research institute, suddenly died without clinical signs. necropsy examination revealed a nodular mass protruding from the left ventral aspect of the larynx, compressing the epiglottis anteriorly. histopathologically, the laryngeal mass was comprised of medium- to large-sized atypical cells. immunohistochemically, these were positive for cd20 and partially positive for cd79α. among the atypical cells were cd3+ t cel ...201931159945
macaca arctoides gammaherpesvirus 1 (strain herpesvirus macaca arctoides): virus sequence, phylogeny and characterisation of virus-transformed macaque and rabbit cell lines.herpesvirus macaca arctoides (hvma) has the propensity to transform macaque lymphocytes to lymphoblastoid cells (mal-1). inoculation of rabbits with cell-free virus-containing supernatant resulted in the development of malignant lymphomas and allowed isolation of immortalised hvma-transformed rabbit lymphocytes (htrl). in this study, the hvma genome sequence (approx. 167 kbp), its organisation, and novel aspects of virus latency are presented. ninety-one open reading frames were identified, of w ...201930291474
gammaherpesvirus rnas come full circle.after an adaptive immune response is mounted, gammaherpesviruses achieve persistence through the utilization of viral noncoding rnas to craft a suitable host cell environment in an immunologically transparent manner. while gammaherpesvirus long noncoding rnas (lncrnas) and micrornas have been recognized for some time and have been actively investigated, a recent spate of reports have now identified repertoires of the circular rna (circrna) class of noncoding rnas in both the lymphocryptovirus an ...201930940699
comparative analysis of gammaherpesvirus circular rna repertoires: conserved and unique viral circular rnas.recent studies have identified circular rnas (circrnas) expressed from the epstein-barr virus (ebv) and kaposi's sarcoma herpesvirus (kshv) human dna tumor viruses. to gain initial insights into the potential relevance of ebv circrnas in virus biology and disease, we assessed the circrnaome of the interspecies homologue rhesus macaque lymphocryptovirus (rlcv) in a naturally occurring lymphoma from a simian immunodeficiency virus (siv)-infected rhesus macaque. this analysis revealed rlcv ortholog ...201930567979
a virome sequencing approach to feline oral squamous cell carcinoma to evaluate viral causative factors.feline oral squamous cell carcinoma (foscc) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (hnscc). hnscc can be broadly divided into human papillomavirus (hpv)-negative cancers and hpv-positive cancers where hpv is the causative agent. previous studies in foscc have used both species-specific and species-nonspecific pcr primers that may be insensitive to the detection of pvs and other viruses that may be divergent from known sequences. virocap is a targ ...202031902496
post-translational protein deimination signatures in serum and serum-extracellular vesicles of bos taurus reveal immune, anti-pathogenic, anti-viral, metabolic and cancer-related pathways for deimination.the bovine immune system is known for its unusual traits relating to immunoglobulin and antiviral responses. peptidylarginine deiminases (pads) are phylogenetically conserved enzymes that cause post-translational deimination, contributing to protein moonlighting in health and disease. pads also regulate extracellular vesicle (ev) release, forming a critical part of cellular communication. as pad-mediated mechanisms in bovine immunology and physiology remain to be investigated, this study profile ...202032325910
alcelaphine herpesvirus 1 genes a7 and a8 regulate viral spread and are essential for malignant catarrhal fever.alcelaphine herpesvirus 1 (alhv-1) is a gammaherpesvirus that is carried asymptomatically by wildebeest. upon cross-species transmission to other ruminants, including domestic cattle, alhv-1 induces malignant catarrhal fever (mcf), which is a fatal lymphoproliferative disease resulting from proliferation and uncontrolled activation of latently infected cd8+ t cells. two laboratory strains of alhv-1 are used commonly in research: c500, which is pathogenic, and wc11, which has been attenuated by l ...202032176737
recombinant epstein-barr virus glycoprotein 350 as a serological antigen.epstein-barr virus (ebv) glycoprotein 350 (gp350) is the most abundant glycoprotein expressed on the ebv envelope, the major target for neutralizing antibodies and also essential for virion attachment to b lymphocytes. several studies have addressed ebv gp350 as a vaccine candidate, but less commonly as a potential antigen for serological assays. the aim of the current study was to develop a diagnostic tool to quantify ebv gp350-specific igg in previously ebv-infected individuals. a construct en ...202032650039
viral opportunistic infections in mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications.allogeneic hematopoietic stem cell transplantation (hsct) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. here, in a mauritian cynomolgus macaque model of fully mhc-matched allogeneic hsct, we report reactivations of cynomolgus polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to hsct-associated human counterparts bk virus, epstein-barr virus, and human cytomegalovirus. viral replica ...202031930750
neutralizing antibodies protect against oral transmission of lymphocryptovirus.epstein-barr virus (ebv) is a cancer-associated pathogen for which there is no vaccine. successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent ebv acquisition. here we assessed whether passively delivered ammo1, a monoclonal antibody that neutralizes ebv in a cell-type-independent manner, could protect against experimental ebv challenge in two animal infection models. when present prior to a high-dose intraveno ...202032724901
antibody-mediated immune subset depletion modulates the immune response in a rabbit (oryctolagus cuniculus) model of epstein-barr virus infection.epstein-barr virus (ebv) is a γ-herpesvirus which infects over 90% of the adult human population. most notably, this virus causes infectious mononucleosis but it is also associated with cancers such as hodgkin and burkitt lymphoma. ebv is a species-specific virus and has been studied in many animal models, including nonhuman primates, guinea pigs, humanized mice, and tree shrews. however, none of these animal models are considered the "gold standard" for ebv research. recently, rabbits have emer ...202032972486
development of an improved epstein-barr virus (ebv) neutralizing antibody assay to facilitate development of a prophylactic gp350-subunit ebv vaccine.no licensed vaccine is available for prevention of ebv-associated diseases, and robust, high-throughput bioanalytical assays are needed to evaluate immunogenicity of gp350 subunit-based candidate ebv vaccines. here we have developed an improved ebv-gfp based neutralization assay for such a vaccine's pre-clinical and clinical validation to measure ebv specific neutralizing antibodies in human donors. the supplementation of guinea pig complement of our previously published high-throughput ebv-gfp ...202032180911
north american big brown bats (eptesicus fuscus) harbor an exogenous deltaretrovirus.bats are the reservoir for a large number of zoonotic viruses, including members of coronaviridae (severe acute respiratory syndrome coronavirus [sars-cov] and sars-cov-2), paramyxoviridae (hendra and nipah viruses), rhabdoviridae (rabies virus), and filoviridae (ebola virus) as exemplars. many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. here, viral metagenomic sequencing o ...202032968009
effect of epstein-barr virus dna on the incidence and severity of arthritis in a rheumatoid arthritis mouse model.we recently demonstrated that ebv dna is correlated with proinflammatory responses in mice and in rheumatoid arthritis (ra) patients; hence, we utilized an ra mouse model to examine whether ebv dna enhances the risk and severity of arthritis and to assess its immunomodulatory effects.202134040613
marek's disease virus meq oncoprotein interacts with chicken hdac 1 and 2 and mediates their degradation via proteasome dependent pathway.marek's disease virus (mdv) encodes a basic-leucine zipper (bzip) protein, meq, which is considered the major mdv oncoprotein. it has been reported that the oncogenicity of meq is associated with its interaction with c-terminal binding protein 1 (ctbp), which is also an interaction partner of epstein-barr virus encoded ebna3a and ebna3c oncoproteins. since both ebna3c and ctbp interact with histone deacetylase 1 (hdac1) and hdac2, we examined whether meq shares this interaction with chicken hdac ...202133437016
plxdc family members are novel receptors for the rhesus monkey rhadinovirus (rrv).the rhesus monkey rhadinovirus (rrv), a γ2-herpesvirus of rhesus macaques, shares many biological features with the human pathogenic kaposi's sarcoma-associated herpesvirus (kshv). both viruses, as well as the more distantly related epstein-barr virus, engage cellular receptors from the eph family of receptor tyrosine kinases (ephs). however, the importance of the eph interaction for rrv entry varies between cell types suggesting the existence of eph-independent entry pathways. we therefore aime ...202133657166
catching viral breast cancer.we have considered viruses and their contribution to breast cancer.202134108009
establishing an induced pluripotent stem cell line from neonatal common marmoset fibroblasts by an all-in-one episomal vector approach.epstein-barr virus (ebv)-based episomal vector system enables persistent transgene expression, which is advantageous for efficient derivation of transgene-free induced pluripotent stem cells (ipscs) without viral transduction. here, we report establishment of an ipsc line from somatic fibroblasts of a neonatal common marmoset monkey (marmoset; callithrix jacchus) using an all-in-one episomal vector that we newly developed. the established ipsc line, named nm-ips, showed standard characteristics ...202134088009
neutralizing antibodies against epstein-barr virus infection of b cells can protect from oral viral challenge in the rhesus macaque animal model.epstein-barr virus (ebv) and related lymphocryptoviruses (lcvs) from nonhuman primates are transmitted through oral secretions, penetrate the mucosal epithelium, and establish persistent infection in b cells. to determine whether neutralizing antibodies against epithelial or b cell infection could block oral transmission and persistent lcv infection, we use rhesus macaques, the most accurate animal model for ebv infection by faithfully reproducing acute and persistent infection in humans. naive ...202134337567
novel gammaherpesvirus associated with primary gastric t-cell lymphoma in a free-ranging giant armadillo in brazil.the number of viral-associated neoplasms reported in wildlife has increased over the last decades, likely because of growing research efforts and a potentially greater burden of carcinogenic pathogens. herein, we describe a primary gastric t-cell lymphoma in one free-ranging giant armadillo (priodontes maximus) from brazilian pantanal infected by a novel gammaherpesvirus, proposed as cingulatid gammaherpesvirus 1 (cihv-1). by chromogenic in situ hybridisation against epstein-barr virus some neop ...202134132049
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