Epstein-Barr virus

؉ T-cell responses are believed to play an important role in the control of human HBV infection. In the present study, HBcAg-specific, HLA-DR13*-restricted CD4 ؉ Th1-type T-cell clones were generated which secreted both gamma interferon and tumor necrosis factor alpha after in vitro antigen stimulation. These HBcAg-specific CD4 ؉ Th1-type T cells were able to lyse HBc peptide-loaded Epstein-Barr virus-transformed lymphoblastoid target cells in vitro. To examine whether these HLA-DR13*-restricted human CD4 ؉ Th1 T cells also display the same cytotoxic effects in vivo, we transferred peripheral blood leukocytes (PBL) derived from HBV-infected donors or an HBV-naïve donor sharing the DR13*, together with the HBcAg-specific CD4 ؉ Th1-type T

An Epstein-Barr virus deletion mutant associated with fatal http://bloodjournal.hematologylibrary.org/content/97/4/835.full.html Updated information and services can be found at: (372 articles) Plenary Papers (577 articles) Immunotherapy Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests

The incidence of neoplastic complications after solid organ transplantation is increasing tremendously probably as the consequence of long term immunosupression. Beside usual risk factors, the oncogenic role of some viruses like Epstein-Barr virus is well established. We report a case of a primitive EBV-induced liver leiomyosarcoma after renal transplantation.

Burkitt’s lymphoma (BL) in Turkish children is commonly associated with Epstein–Barr virus (EBV) infection. The C-terminus of the latent membrane protein 1 (LMP-1) of EBV is essential for transformation and the 30-bp deletion detected in this region has been implicated to be associated with a more aggressive malignant phenotype. To understand the molecular mechanisms underlying EBV pathogenesis in BL of

Background: Multiple sclerosis (MS) is a neurological disorder with a highly characteristic disease distribution. Prevalence and incidence in general increase with increasing distance from the equator. Similarly the female to male sex ratio increases with increasing latitude. Multiple possible risk factors have been hypothesised for this epidemiological trend, including human leukocyte antigen allele frequencies, ultraviolet exposure and subsequent vitamin D levels, smoking and Epstein-Barr virus. In this study we undertook a study of medical records across Scotland on an NHS health board level of resolution to examine the epidemiology of MS in this region.

We show clear evidence for direct infection of various human epithelial cells by Epstein-Barr virus (EBV) in vitro. The successful infection was achieved by using recombinant EBV (Akata strain) carrying a selective marker gene but without any other artificial operations, such as introduction of the known EBV receptor (CD21) gene or addition of polymeric immunoglobulin A against viral gp350 in culture. Of 21 human epithelial cell lines examined, 18 became infected by EBV, as ascertained by the detection of EBV-determined nuclear antigen (EBNA) 1 expression in the early period after virus exposure, and the following selection culture easily yielded a number of EBV-infected clones from 15 cell lines. None of the human fibroblasts and five nonhuman-derived cell lines examined was susceptible to the infection. By comparison, cocultivation with virus producers showed approximately 800-fold-higher efficiency of infection than cell-free infection did, suggesting the significance of direct c...

Acute acalculous cholecystitis (AAC) comprises 5% to 10% of all cases of acute cholecystitis in adults and appears to be even less frequently diagnosed in children. The diagnosis of AAC is established upon some clinical, laboratory, and ultrasonographic findings, which ...

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with rarer neurological presentation. When this occurs, diagnosis may be delayed. This report aims to call attention to clinical, laboratory, and radiological features that should prompt the correct diagnosis. A 13-yearold girl presented with progressive increase in intracranial pressure and ataxia. MRI showed a diffuse tumor-like swelling of the cerebellum with tonsillar herniation and patchy white matter post-contrast enhancement. Regression of swelling with steroids ruled out glioma and medulloblastoma, and brain lymphoma was considered. Diagnosis of HLH was reached 2 months after onset when uncontrolled fever and severe elevation of liver enzymes occurred. Two bone marrow biopsies were needed to demonstrate hemophagocytosis. Familial HLH was confirmed by perforin gene mutations. Bone marrow transplantation was performed. The early diagnosis of HLH may be life saving. Awareness of the disease is necessary to investigate its characteristic findings, thus avoiding a delay in diagnosis.

Expression Pattern of Epstein-Barr Virus Latent Genes in Cell ... Lines Derived from Oral Squamous Cell Carcinoma ... Abu Mohammad Eahsan Rasul1,2, Ieyoshi Kobayashi2, Tamotsu Kiyoshima2, Kou Matsuo2, Masamichi Ohishi1 and Hidetaka Sakai2 1Department of Oral ...

Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness ( _ VO 2max ) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61 yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28À) CD4+ (B = 1.00; 1.02) and CD8+ (B = 0.429; 1.02) T-cells and inversely associated with naïve (KLRG1À/CD28+) CD4+ (B = À1.000) and CD8+ (B = À0.993) T-cells. _ VO 2max was inversely associated with senescent CD4+ (B = À0.97) and CD8+ (B = À0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for _ VO 2max , while the association between _ VO 2max and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted _ VO 2max revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. _ VO 2max was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of _ VO 2max were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system.

Infections are considered to be an important cause of unexpected death in children. It has also been assumed that respiratory viruses are involved in the genesis of sudden infant death syndrome (SIDS). The Spanish National Institute of Toxicology and Forensic Sciences act as the forensic reference centre for Spain. We analyse the experience of this centre in the virological study of 64 cases of sudden children death where viral serology, virological cultures, herpesviruses polymerase chain reaction (PCR) and electron microscopy were performed. According to pathological findings, death could only be attributed to an adenovirus infection in one amygdalitis with upper airways stenosis and asphyxia. Human herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile, 85.9% of the cases yielded negative viral results. Twenty-eight infants were finally categorised as SIDS. Pathological findings of infection were detected in 12 patients despite the negativity of viral analyses. Although viral infection is an uncommon cause of sudden children death, a complete microbiological investigation will help to solve the puzzle of SIDS. Definitive guidelines for microbiological analyses need to be updated whilst new pathogens are discovered or new techniques are implemented in order to clarify unsolved cases. #

Human interleukin-10 (h-IL-10) is a pleiotropic cytokine with stimulatory activity on B-Iymphocytes. Recent evidence indicates that infection with Epstein-Barr virus (EBV) induces h-IL-10 production in B-cells and that this cytokine may contribute to EBV-induced B-cell transformation. It is not known whether h-IL-10 induction by EBV correlates with distinct phenotypic features of the infected cells or with the expression of particular viral genes. We have approached these questions by investigating the expression of h-IL-10 mRNA in a panel of B-cell lines including: in vitro EBV-transformed lymphoblastoid cell lines (LCLs), EBV-carrying Burkitt lymphoma (BL) lines, EBV-negative BL lines and their sublines infected with different EBV strains, or transfected with the transformation-associated viral gene. h-IL-10 mRNA was detected by reverse-transcriptase-assisted (RT)-PCR in a subset of EBV-negative BLs and in all FBV-positive BL lines and LCLs investigated except Daudi. This cell line carries an EBV nuclear antigen (EBNA)-2 gene-defective virus strain. h-IL-10 mRNA was induced by conversion of 3 EBV-negative and h-IL-10-negative BL lines (BL41, BL47 and BL49) with the transforming, B95.8-derived EBV strain. P3HR-1 virus convertants that do not express the viral EBNA-2 and the EBV latent membrane protein (LMP)-1, and fail to progress towards a LCL-like cell phenotype, showed no evidence of h-IL-10 up-regulation. Expression of LMP1 was sufficient to induce h-IL-10 mRNA in transfected sublines of the EBV-negative DG75 and BL41 cell lines, whereas expression of EBNA1, 2, 5 or 6 had no effect. h-IL-10 was detected in the culture supernatants of the LMP1 transfectants by specific ELISA assays. The present findings confirm the role of LMP1 in the transactivation of a wide variety of cellular genes which may be involved in EBV-induced B-cell transformation. © 1994 Wiley-Liss, Inc.

Epstein-Barr virus (EBV) is world widely distributed. About 98% of adults are infected with EBV. Early
childhood is shown to be infected with EBV, EBV possesses many proteins having sequence and functional
homology with many human proteins. EBV open reading frames such as BRLF1, BRCF1, BARF1, BHRF1 and
BILF1 program the host for lytic and latent states as well as acute and chronic infections. EBV can induce
production of some cytokines such as IL-15 (with TNF-α), IL-10, and IL-6. On conclusion, much organized efforts
in the future studies are needed for EBV to be controlled as with the time pass, our bodies will become saturated
with this virus. our recommendations are retrospective identification of the previously discovered viruses with
electron microscopy, followed by whole genome sequencing, sequencing of whole glycoprotein B gene for any
suspected herpesvirus, extensive studies for autoimmune antibodies to know if they are idiopathic or for enveloped
EBV or its components and finally considering feces one of the modes for infection.

Increased extraglandular aromatization has been reported as the cause of familial gynecomastia. We studied a kindred with aromatase excess inherited in an autosomal dominant manner, in which affected males had heterosexual precocity and/or gynecomastia, and affected females had isosexual precocity and/or macromastia. The propositus was a 9-yr-old boy with gynecomastia. His 7.5-yr-old sister had precocious puberty, and their father and

The effects of 50 Hz electromagnetic fields (EMFs) on the expression of the c-myc oncogene, known to be involved in normal cell proliferation and possibly also in tumor processes, were investigated in nonsynchronized human lymphoid cells immortalized by Epstein-Barr virus. Viral injury to such cells makes them a good model for exploring the possible cancer-promoting effects of 50 Hz magnetic fields. Parallel experiments were conducted on human HL60 leukemic cells. Cells were exposed to sinusoidal 50 Hz EMFs at 10 pT or 1 mT for 20 min, 1 h, 24 h, or 72 h. Exposure was performed either immediately after refeeding or 1.5 h after refeeding. C-myc transcript values were assessed by Northern blot analysis and normalized to those of the noninducible gene GaPDH. No statistically significant difference between the c-myc transcript levels of control and exposed cells was found in lymphoid or leukemic cells under our experimental conditions, either after short exposures of 20 min and 1 h or after longer exposures of 24 and 72 h. Other experiments were carried out with pseudosynchronized cells in an attempt to establish whether cells were especially sensitive to 50 Hz magnetic field exposure in any particular phase of the cell cycle. Accordingly, cells were pseudosynchronized in GO/GI by serum deprivation and exposed for 20 min to a 50 Hz magnetic field, at 10 pT for lymphoid cells and 1 mT for HL60 cells. No significant difference was observed between the c-myc transcript levels of control and exposed cells for either of the synchronized cell types. These results for synchronized cells correlated with those for nonsynchronized cells. 01995 Wiley~LiYq, Inc.

An HLA-mismatched donor and a T-cell-depleted graft are known risk factors for Epstein-Barr virus (EBV) reactivation after stem cell transplantation. We studied the frequency and outcome of serum EBV DNA levels in patients transplanted with an unmanipulated graft from an HLA-identical donor.

We describe the first case of an Epstein-Barr virus (EBV)-associated natural killer-large granular lymphocyte (NK-LGL) leukemia in the United States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EBV infection after a blood transfusion as indicated by a rise in serum antibody titers. Peripheral blood and bone marrow aspirate smears demonstrated increased LGLs. Flow cytometry showed that these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related clones with multiple copies of a modified 7 marker chromosome. Death followed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadenitis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system vasculitis with perforation of the transverse colon. Epstein-Barr virus transcripts were identified in lympho...

About 15-20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus, contribute to cancer development. Human tumorassociated viruses have evolved multiple molecular mechanisms to disrupt specific cellular pathways to facilitate aberrant replication. Although oncogenic viruses belong to different families, their strategies in human cancer development show many similarities and involve viral-encoded oncoproteins targeting the key cellular proteins that regulate cell growth.

Six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster (VZV), Epstein-Barr (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6). When herpesviruses infect the central nervous system (CNS), the clinical presentation is non-specific and often confounding. The clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagnosis and treatment rely heavily on neuroimaging. This review focuses on the spectrum of cerebral manifestations caused by these viruses, particularly on non-congenital presentations. Recent advances in our understanding of these viruses are discussed, including new polymerase chain reaction techniques that allow parallel detection, which has improved our recognition that the herpesviruses are neurotropic and involve the CNS more often than previously thought. Evolving knowledge has also better elucidated viral neuropathology, particularly the role of VZV vasculitis in the brain, HHV-6 in febrile seizures, and herpesvirus reactivation in immunosuppressed patients. The virology, clinical course, and CNS manifestations of each virus are reviewed, followed by descriptions of neuroimaging findings when these agents infect the brain. Characteristic but often subtle imaging findings are discussed, as well as technical pearls covering appropriate use of MRI and MRI adjuncts to help differentiate viral infection from mimics.

Transfusion Clinique et Biologique 18 (2011) 516-526 Review From whole blood to component therapy: The economic, supply/demand need for implementation of component therapy in sub-Saharan Africa Du sang total aux médicaments dérivés du sang : nécessité économique de l'utilisation des dérivés du sang en Afrique sub-saharienne Abstract

Primary cultures of epithelial cells were grown from tonsils of patients with diseases not related to EBV. The cells were implanted with EBV receptors and exposed to EBV of the transforming (B95-8, AG-876) and nontransforming (P3HR-1) strains. The EBV-infected and control cells were pulsed with [35S]methionine at 18-24 h after infection, and cell extracts were prepared for immunoprecipitation with anti-EBV sera and analysis by gel electrophoresis and autoradiography. About 20 EBV-determined proteins ranging from 22 to 185 kDa were detected in P3HR-1 virus-infected epithelial cells. Only a few polypeptides were detected in extracts of cells infected with AG-876 virus while no EBV-specific proteins were immunoprecipitated from extracts of B95-8 virus-infected cells. These results demonstrate that the system of EBV receptor-implanted normal human epithelial cells can be used for direct biochemical analysis of EBV infection in the epithelial tissue.

Monitoring of Epstein–Barr virus (EBV) infec-tion and reactivation in immunocompromized patients (eg, after organ or bone-marrow trans-plantation) is based mainly on serological assays and detection of viral DNA. For further character-ization of virus reactivation and monitoring of ...

Hodgkin's disease represents a phenotypically and genotypically heterogeneous lymphoma of CD30-positive tumour cells. Infection of the putative tumour cell population with Epstein-Barr virus (EBV) represents the most common genetic abnormality detectable in HD, yet the role of EBV in the pathogenesis of HD is only poorly understood. In virusassociated HD cases, monoclonal EBV genomes are detectable in all Hodgkin and Reed-Sternberg (HRS) cells, indicating that EBV infection takes place before expansion of the HRS cell population and, by implication, supporting the concept of a monoclonal origin of HRS cells. EBV infection does not define a distinct subgroup of HD but is detectable in different histotypes and in HRS cells expressing lymphocyte differentiation antigens of different cell lineages. Through the EBV-encoded protein, LMP1, the virus may superimpose an activated phenotype on genotypically immature lymphocytes. EBV-induced modulation of the cytokine expression pattern of HRS cells may contribute to the local inhibition of EBV-specific immunity observed in EBV-positive cases.

Background: the genomes of human Kaposi's sarcoma-associated herpesvirus (KSHV) display several levels of DNA sequence heterogeneity and subgrouping that show distinctive clustering patterns in related human populations. The four major subtype patterns for the hypervariable ORF-K1 protein correlate closely with the principal diasporas resulting from the migration of modern humans out of East Africa and suggest that KSHV is an ancient human virus that is transmitted primarily in a familial fashion with consequent very low recombination rates. However, chimeric www.elsevier.com/locate/jcv : S 1 3 8 6 -6 5 3 2 ( 0 1 ) 0 0 2 0 5 -0 J. Zong et al. / Journal of Clinical Virology 23 (2002) 119-148 120 genomes have also been detected, especially with regard to the presence of P versus M alleles of the ORF-K15 gene. Objecti6es: to understand further the genetic organization and evolutionary history of KSHV, especially with regard to possible new subtypes, recombinant genomes, constant region loci and clustering in particular ethnic groups or among classic versus epidemic cases in the same geographic area. Study design: direct PCR DNA sequencing was carried out on the ORF-K1 and ORF-K15 genes at the extreme left and right hand sides, as well as on six other internal loci of diagnostic samples collected from 70 new KSHV-positive patients in Israel, South Korea, Sicily, Scandinavia, Brazil, Uganda, South Africa and the US. Results and conclusions: our overall results from more than 135 KSHV genomes from many different human population groups now provides evidence for seven distinct subtypes of KSHV genomes (referred to as A/P, B/P, C/P, D/P, M, N and Q). However, the two most closely related subtypes (A/P and C/P) are only differentiated at the LHS side of the genome, and the three most distantly related forms (M, N and Q) appear to exist only as small chimeric segments that are remnants from the RHS of more ancient forms of the virus. By analyzing multiple conserved loci across the B subtype genomes that predominate in sub-Saharan Africa, we can also now recognize three to four distinct B genome subgroups with varying patterns of inter and intratypic mosaicism. Analysis of classic KS genomes from Israel has revealed that the ORF-K1 clade referred to as A1% predominates in Ashkenazi Jewish immigrants from Russia, whereas C2 and C6 variants predominate in North African Sephardi Jews. A variety of chimeric genomes containing C2 or C3 ORF-K1 genes are disseminated among classic KS cases throughout Europe and Asia including Israel, Sicily, Scandinavia, South Korea, and Taiwan. Comparison of the genomes from classic versus AIDS-associated KSHV in the US indicates that it was derived originally by reactivation and spread of a subset of the endogenous viruses carried by descendants of immigrants from endemic areas of Northern and Eastern Europe, the Mediterranean and sub-Saharan Africa.

Productive infection and replication of herpesviruses usually occurs in growth-arrested cells, but there has been no direct evidence in the case of Epstein-Barr virus (EBV), since an efficient lytic replication system without external stimuli does not exist for the virus. Expression of the EBV lytic-switch transactivator BZLF1 protein in EBV-negative epithelial tumor cell lines, however, is known to arrest the cell cycle in G 0 /G 1 by induction of the tumor suppressor protein p53 and the cyclin-dependent kinase (CDK) inhibitors p21 WAF-1/CIP-1 and p27 KIP-1 , followed by the accumulation of a hypophosphorylated form of the Rb protein.

The reaction of o-phenylene diamine and ethyl oxamate is reinvestigated and led to 3-aminoquinoxalin-2(1H)-one rather than benzimidazole-2-carboxamide as was previously reported. The structure of the obtained quinoxaline has been confirmed by X-ray. The anti-tumor activity of synthesized quinoxalines 1–21 has been evaluated by studying their possible inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds 1–21, compounds 12, 8, 13, 18, 17 and 19, respectively, demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity and their effects being stronger than that of a representative control, oleanolic acid. Furthermore, compound 12 exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The result of the present investigation indicated that compound 12 might be valuable as a potent cancer chemopreventive agent. Moreover, the molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.Ligand interaction and the binding mode of compound 17 with c-kit receptor, it exhibited 3 H-bonds with the amino acids in C-kit two of them with CYS 673 and one with ASP 677, the hydrogen bonds formed colored in green.► New quinoxalines derivatives have been synthesized to evaluate their cancer chemopreventive activity. ► The inhibitory effects of compounds 1–21 on Epsteine Barr virus early antigen (EBV-EA) activation induced by TPA have been studied. ► The in vivo two-stage carcinogenesis test of compound 12 was studied. ► The synthesized compounds docked into c-kit protein-tyrosine kinase.

The term "gray-zone" lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and Epstein-Barr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panel's proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters.