cord-000718-7whai7nr 2012 Method: We analyzed consecutive gastric cancer cases in terms of AMACR immunohistochemical expression and clinical/pathological characteristics and followed patients'' postoperative history. Results: Histological, immunohistochemical and molecular examination revealed non-neoplastic lymphadenopathy with atypical paracortical T-cell hyperplasia with immunoblastic reaction in the former and burnt-out histiocytic pattern in the latter, both falling into a broad spectrum of reactive lymph node changes associated with Still''s disease. Method: We have thus collected, from our two Institutions a large number (45 cases) of cancers showing the histological definition of adenosquamous carcinomas according to the WHO criteria and performed gene analysis for k-RAS (codons 12, 13) and EGFR (codons 18, 19 and 21) mutations. Objective: We previously identified amplified fibroblast growth factor 1 (FGFR1) as a therapeutic target for small molecule inhibitor (SMI) therapy in squamous cell lung cancer (L-SCC), resulting in currently running clinical trials treating patients with stage III disease. cord-000849-rrezynbs 2012 cord-000914-d0bk9gu5 2013 In this article, we highlight emerging evidence supporting the proposition that the signaling pathways anchored by Basigin/CD147 and CD36, two of the known host receptors that control Pf invasion and cyto-adherence, respectively, are also targets for functional subversion by Kaposi''s sarcoma (KS)-associated herpesvirus (KSHV), an inherently persistent cancer-associated herpesvirus that is prevalent in malaria-endemic regions. Remarkably, we have also discovered that cross-linking of CD36 on the surface of KSHV-infected cells with MC179, a recombinant peptide derived from the CIDR1α domain of PfEMP-1 that normally interacts with CD36 to mediate cyto-adherence (Ockenhouse et al., 1989 (Ockenhouse et al., , 1991 Baruch et al., 1997) , not only upregulated CD36 expression (Figure 2A ) but also reactivated the virus from latency through transcriptional activation of KSHV RTA (Figure 2B) , and that the molecular mechanisms that control this process overlap with those that putatively regulate PfEMP-1dependent EBV reactivation from latently infected cells (Chene et al., 2007) . cord-001927-jt81i0uc 2015 Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBVassociated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBVassociated tumors. The diseases include those of a lymphocytic nature, namely infectious mononucleosis, Hodgkin''s disease (HD), Burkitt''s lymphoma (BL), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas and those of an epithelial nature such as oral hairy leukoplakia (OHL), nasopharyngeal carcinoma (NPC) and undifferentiated gastric carcinoma [5] . Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease Epstein-Barr virus (EBV) gene expression in EBVpositive peripheral T-cell lymphomas Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells cord-004675-n8mlxe7p 2019 However, the mean infusion rate per site was similar between patients aged <18 years ( XMEN disease (X-linked Immunodeficency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a primary immune deficiency caused by mutations in MAGT1 and characterized by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia. We present the case of a 1-year old Hispanic infant with a pathogenic variant in MAGT1 gene that clinically manifested with early Pneumocystis jirovecii and cytomegalovirus (CMV) interstitial pneumonia, and EBV chronic infection with good response to intravenous immunoglobulins supplementation without hematopoietic stem cell transplantation or gene therapy. Chief, Laboratory of Clinical Immunology and Microbiology, IDGS, DIR, NIAID, NIH, Bethesda, MD, USA Hypomorphic Recombination Activating Gene 1 (RAG1) mutations result in residual T-and B-cell development in both humans and mice and have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI). cord-005435-onghg1o8 2003 title: Prolonged gene expression in mouse lung endothelial cells following transfection with Epstein–Barr virus-based episomal plasmid In this study, we show that pulmonary gene transfer via cationic lipidic vectors can be significantly improved using an Epstein–Barr virus (EBV)-based expression plasmid. Systemic administration of cationic liposomes followed by the EBV-based plasmid led to gene expression in the lung that lasted for more than 3 weeks. Prolonged and high levels of gene expression can also be obtained in primary mouse lung endothelial cells (MLEC) following lipofection with an EBV-based plasmid. In the current study, we investigate whether in vitro and in vivo gene transfer to mouse lung endothelial cells (MLEC) can be significantly improved using an EBVbased expression plasmid. Furthermore, sequential injection of DOTAP:cholesterol liposomes and pGEG.GL3 led to a significantly higher level of gene expression in the lung than complex injection (Figure 2b ). Figure 5 Prolonged gene expression in primary lung endothelial cells following lipofection with an EBV-based plasmid. cord-005453-4057qib7 2019 To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective, observational cohort study enrolled in 21 HID-SCT and 13 MSD-SCT recipients. The aim of this study is to identify the prognostic impact of pre-transplant TIM3 levels on early and late transplant related complications as well as post-transplant relapse and survival Methods: A total of 177 hematopoietic stem cell transplantation (HSCT) recipients with an initial diagnosis of acute leukemia [median age: 36(16-66) years; male/ female: 111/66] were included in the study. cord-005460-ezrn8cva 2017 Still the optimal combination of immunosuppressive agents with PTCy should be elucidated for different types of SCTs. We report the 2-year update of the prospective NCT02294552 single-center trial that evaluated risk-adapted graft-versushost disease (GVHD) prophylaxis with PTCy in related, unrelated and haploidentical SCTs. 200 adult patients (median age 32 y.o., range: 18-62) with hematologic malignancies, including AML (47.5%), ALL (26.5%), CML (10.5%), MDS (4%), and lymphomas (11.5%), were enrolled in the study. Long-term follow-up from the prospective randomized phase III multicenter trial comparing a standard GvHD prophylaxis with cyclosporine A and methotrexate with or without additional pretransplant ATLG (Grafalon, previously ATG-FRESENIUS S) (given 20 mg/kg/day, days − 3 to − 1) in unrelated donor hematopoietic cell transplantation after myeloablative conditioning resulted in a significant reduction of acute and chronic GvHD without compromising relapse rate and survival [1, 2, 3] . cord-006466-e1phpqes 2018 Whole exome sequencing revealed a heterozygous mutation, previously reported (c.1425+1G>T) Conclusions: In summary, this report emphasizes the suspicion of a combined immunodeficiency in the presence of multiple abscesses by Mycoplasma, the usefulness of rDNA 16s in order to achieve proper Objectives: We describe a 15-year-old male patient with novel heterozygous mutation of EP300 gene; his first manifestations were initially characterized by infections, cytopenia and hypogammaglobulinemia suggesting a Common Variable Immunodeficiency (CVID), but later on, persisting lymphopenia was suggestive of a combined immunodeficiency. Conclusions: Close monitoring of immune function in early life for patients with CHH and CID as well as the availability of suitable donors assists in determining management, including HSCT Introduction/Background: Leukocyte Adhesion Deficiency (LAD) represents a group of distinct inherited disorders, which inhibit the normal extravasation of neutrophils and their recruitment to sites of infection or inflammation. cord-009997-oecpqf1j 2018 Completed cranial radiation and proceeded to allogeneic stem cell transplant with unrelated cord marrow donor and is disease free at approximately day +200.Case 2: 5 year-old female diagnosed with FLT3 and MLL negative AML and completed treatment per COG AAML1031 study on the low risk arm without Bortezomib. Design/Method: This study was a retrospective chart review that included patients 3 to 23 years old with sickle cell disease type SS and S 0 followed at St. Christopher''s Hospital for Children. Background: Hydroxyurea, chronic blood transfusion, and bone marrow transplantation can reduce complications, and improve survival in sickle cell disease (SCD), but are associated with a significant decisional dilemma because of the inherent risk-benefit tradeoffs, and the lack of comparative studies. Brown University -Hasbro Children''s Hospital, Providence, Rhode Island, United States Background: Despite clinical advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant source of disease-related morbidity. cord-015306-us58wwmp 2013 The incidence of renal involvement varies from 20 to 60% and there have been some reports showing that nephritis might be related to an older age at onset, persistent purpura (> 1 month), severe abdominal pain, and relapsing disease.Recently, several studies have shown that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, resulting in the formation of the circulating immune complexes and their mesangial deposition causing renal injury in HSP nephritis and serum galactose-deficient IgA1 levels were highly inherited in children with HSP nephritis.Regarding the treatment of HSP, one randomized double-blinded controlled study recently showed that patients with abdiminal pain or arthralgia may benefit from early treatment with prednisone, but the drug has not been proven to be capable of preventing the development of renal symptoms. cord-016255-kkko1xne 2011 cord-016932-bej10xbf 2018 cord-018017-c8myq6bi 2018 Numerous emerging infections caused by viral agents have imposed high impact on human survival (Table 3 .3). The apparent success of these viruses is that as they move from reservoir hosts to humans and as humans become immune to the initial infection, the population of diverse genomes offers multiple chances to adapt by finding a "fit" genome version which can propagate until the next transition requiring adaption. Human T-cell Lymphotropic Virus (HTLV-1) HTLV-1 is a single-stranded RNA retrovirus, defined by their use of reverse transcriptase, a polymerase, that makes a DNA copy of the RNA 7 kb viral genome. If we combine cardiovascular events and neoplasia caused by infection, then infectious disease is the most significant threat to human life and qualifies as the area of greatest impact. Adeno-associated Virus (AAV) is a single stranded DNA virus that infects humans but are not known to cause disease. is a 5229 base double-stranded DNA virus infecting less than 5 percent of the human population. cord-022472-q2qtl26d 2009 • Solid organ transplant recipients who are naïve (seronegative) and receive an organ from a seropositive donor (D+/R−) • Solid organ transplant recipients who are seropositive (R+) and receive antilymphocyte antibodies or other intensive immune suppression (e.g., for graft rejection) Symptoms, fever/neutropenia mo (or valacyclovir 500 bid or acyclovir 400 tid) Use of CMV-negative or leukocyte-filtered blood Status unknown with ALS Intravenous ganciclovir 5mg/kg iv for first dose and QD (corrected for renal function) until sero-status determined. • End organ damage (e.g., BK polyomavirus nephropathy, cryoglobulinemia, or cirrhosis from HCV-HBV being relatively well managed at present) • Malignancy (post-transplantation lymphoproliferative disease [PTLD] due to EBV, skin, or anogenital cancer due to papilloma viruses) • Acquired immunodeficiency syndrome (HIV/AIDS) The third group of patients (~10% of all recipients) has less than satisfactory allograft function and requires excessive amounts of immunosuppressive therapy for recurrent graft rejection. cord-022888-dnsdg04n 2009 Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cord-023747-mvq6353a 2009 The epidemiologic evidence points to three environ­mental risk factors—infection with the Epstein-Barr virus (EBV), low levels of vitamin D, and cigarette smoking—whose association with multiple sclerosis (MS) seems to satisfy in varying degrees most of the criteria that support causality, including temporality, strength, consis­tency, biologic gradient, and plausibility. As discussed in this chapter, epidemiologic evidence points to three environmental risk factors-infection with the Epstein-Barr virus (EBV), low levels of vitamin D, and cigarette smoking-whose association with multiple sclerosis (MS) seems to satisfy in varying degrees most of the criteria that support causality, including temporality (i.e., the cause must precede the effect), strength, consistency, biologic gradient, and plausibility. 28 Studies within the United States have also supported a decreased risk of MS among migrants from northern (>41° to 42° N), Australia and New Zealand Europe Figure 4-1 Worldwide prevalence estimates of multiple sclerosis. cord-023854-w8kx5n8k 2019 Anschließend dringt das Virus in die Nervenendigungen von peripheren sensorischen Nerven ein und wandert in ihnen retrograd bis zu den spinalen Hinterstrangganglien (bei HSV-1 meist Ganglion des N. Schleimhaut (Dermatom), wo es zur lokalen Virusvermehrung und Ausbildung von Bläschen kommt: Herpes zoster bei VZV, Herpes labialis oder genitalis bei HSV Die Infektion beginnt mit unspezifischen Symptomen (Fieber, Kopfschmerzen, Krankheitsgefühl) . VZV kann bei nachlassender zellulärer Immunität sowie durch noch unbekannte Mechanismen jederzeit reaktiviert werden: VZV wandert nun entlang der sensorischen peripheren Nerven anterograd an die Hautoberfläche, wo es im Bereich der betroffenen Dermatome zur Virusvermehrung mit Bläschenbildung (Herpes zoster) kommt. Inwieweit diese Komplikationen tatsächlich ursächlich nur durch HHV-6, oder möglicherweise erst in Verbindung mit zusätzlichen Infektionen (HIV, CMV und andere Herpesviren) hervorgerufen werden, ist derzeit nicht bekannt. Die Entwicklung eines Hydrops fetalis nach einer mütterlichen (und fetalen) Parvovirus-B19-Infektion ist insgesamt selten, sie liegt bei ca. cord-024651-578c9ut5 2020 Abstract/Case Report Text Introduction: Mutations in the gene encoding signal transducer and activator of transcription 3 (STAT3) cause autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES) characterized by recurrent skin and sinopulmonary infections, atopic dermatitis, and elevated serum immunoglobulin E (IgE) levels. Objective: The purpose of this study is to increase awareness and improve diagnosis of primary immune deficiency (PID) in the heterogenous group of patients with autoimmune cytopenia (AIC) by identifying clinical characteristics and laboratory biomarkers that distinguish those with underlying PID, disease activity and guide mechanism-based targeted therapy. 7 Chief, Laboratory of Clinical Immunology and Microbiology/National Institute of Allergy and Infectious Diseases, NIAID/National Institutes of Health, NIH Abstract/Case Report Text We have previously used the artificial thymic organoid (ATO) system, based on the 3D aggregation and culture of a delta-like canonical Notch ligand 4-expressing stromal cell line (MS5-Dll4) with CD34+ cells, to study T cell differentiation from CD34+ cells obtained from patients carrying defects that are intrinsic to hematopoietic cells (RAG1-2, AK2, IL2RG) or that affect thymus development (DiGeorge syndrome). cord-031252-ji0ef0by 2020 cord-256130-zhlvvuj4 2018 Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. The aim of the present study was to evaluate levels of TTV and EBV in relation to the frequency of infectious events and acute rejections over time in a prospective manner in a single-center cohort of lung-transplanted patients. The total nucleic acid content was isolated from serum or whole blood samples and analyzed for TTV-, EBV-, and CMV-DNA load by real-time PCR. Comparison of TTV-and EBV-DNA levels in lung transplant recipients who received either Tacrolimus-or Cyclosporinebased therapy revealed that Cyclosporine-treated patients had significantly lower TTV-DNA levels in serum at month 6 post-LTx and onwards, compared with the Tacrolimustreated patients (Figure 1 ). However, we found no association between either TTV-or EBV-DNA load and infectious events or acute rejections, which suggests a limited clinical applicability as biomarkers predicting short-term outcomes related to the net state of immunosuppression. cord-257271-jzmwy4yi 2008 cord-257299-z9u12yqb 2009 Common childhood viral infections, such as measles and mumps are probably an unrecognized cause of acute or progressive damage to hearing [5] . Measles infection can be avoided by administering a reduced, live-virus vaccine to children between the ages of 12 and 15 months (MMR). The etiology of the acute forms in the respiratory airways is, initially, of a viral nature in most patients, with later, secondary bacterial infections on the mucous lesions caused by the viral agents [31] . Herpangina is an extremely contagious illness caused by a coxackievirus characterized by a presence of a vesicular exanthema at the velopharyngeal mucous level and acute or croup laryngotracheitis [38] [39] [40] [41] when viral infections are associated. The most common manifestation of the primary infection of this organism is infective mononucleosis (IM), a sometimes acute, but often asymptomatic clinical syndrome which more often strikes children, adolescents, and young adults [82] . Viral etiology and epidemiology of acute lower respiratory tract infections in children cord-259194-9zllvfqb 2011 cord-261251-ylvqxpba 2013 BACKGROUND: Hemophagocytic syndrome (HPS) is clinically defined as a combination of fever, liver dysfunction, coagulation abnormalities, pancytopenia, progressive macrophage proliferation throughout the reticuloendothelial system, and cytokine over-production, and may be primary or secondary to infectious, auto-immune, and tumoral diseases. In the case of severe EBV-related HPS, the introduction of immuno-chemotherapy and, if necessary, allogenic stem cell transplantation has radically changed the history and prognosis of the disease: in such cases, the optimal treatment strategy can be centred on immunosuppressive medications that inhibit overactive T and NK cell responses (i.e. corticosteroids, cyclosporine A, intravenous immunoglobulin, anti-thymocyte globulins, etoposide, rituximab, and plasma or blood exchange transfusions) [38, 39] . Clinicopathological study of severe chronic active Epstein-Barr virus infection that developed in association with lymphoproliferative disorder and/or hemophagocytic syndrome Quantitative analysis of cell-free Epstein-Barr virus genome copy number in patients with EBV-associated hemophagocytic lymphohistiocytosis Penicilliosis-associated hemophagocytic syndrome in a human immunodeficiency virus-infected child: the first case report in children cord-266218-r6xg9zts 2018 cord-268207-4dabwcfi 2010 cord-275903-sfrpfy5g 2016 In this article, we will discuss the utility of targeting EBV gene products, the viral episome, and whole virus for research, screening, diagnostic, and future treatment of NPC ( Fig. 1 ). Given the non-integrative characteristic of the EBV episome and its ability to accommodate large transgene insertion, the use of EBV episomal vector had been extended to genetic studies, protein production, gene therapy, and iPSCs generation. Epstein-Barr virus vector-mediated gene transfer into human B cells: potential for antitumor vaccination Highly efficient suicide gene expression in hepatocellular carcinoma cells by Epstein-Barr virus-based plasmid vectors combined with polyamidoamine dendrimer Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma Plasma Epstein-Barr virus (EBV) DNA: role as a screening test for nasopharyngeal carcinoma (NPC)? cord-277096-zvb7n9wo 2018 cord-281086-fmftr5jn 2020 cord-281404-5a8au32c 2013 The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Here we report that induction of the productive virus cycle has no appreciable effects on the global levels of protein ubiquitination but is accompanied by a BPLF1-dependent decrease of cullin neddylation and stabilization of nuclear CRL substrates. The Akata-Bx1 cell line was used to study the contribution of the Ub-and NEDD8-specific deconjugase activities of the EBV large tegument protein BPLF1 to the productive virus cycle. In order to assess whether this regulatory interaction may operate during virus replication, the productive cycle was induced in Akata-Bx1 cells transiently transfected with plasmids expressing Myc-tagged CAND1 or the CAND1 Nterminus that compete for BPLF1 binding to cullins, or, as controls, the CAND1 C-terminus that binds to the opposite end of the cullin scaffold, and the empty vector ( Figure 5A ). cord-284235-ae37re3f 2011 METHODS: To determine the prevalence of EBV in the tonsils and adenoids of the United Arab Emirates (UAE) nationals and to provide a basis for understanding the origin and biology of EBV-infected cells, the immunophenotype of all EBV-infected cells in 46 tonsils and 46 adenoids was determined by EBER in situ hybridization and immunohistochemistry with monoclonal antibodies to T cells (CD3), B cells (CD20), and epithelial cells (cytokeratin AE1/AE3), as well as immunostaining with antibodies to EBV latent membrane protein-1 (LMP-1). In our study we do not identify EBV in epithelial cells of tonsils and adenoids whereas it is only detected in B lymphocytes. Detection of Epstein-Barr virus in tonsillar tissue of children and the relationship with recurrent tonsillitis cord-288945-c9ow1q5c 2019 cord-289690-af6lsj1g 2015 BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic celland B-lymphopenia, irrespective of severity of the clinical phenotype. Defects of transcription factor GATA-2 have recently been identified in a few overlapping phenotypes associated with myeloid malignancies: dendritic cell, monocyte, B-and NK-cell deficiency; MonoMAC syndrome (monocytopenia with Mycobacterium avium complex infections); Emberger syndrome (early onset primary lymphedema, multiple warts, sensorineural deafness, dysmorphism); and familial MDS/AML with no additional known phenotype. We present an adolescent male with GATA-2 deficiency and early manifestation of diffuse parenchymal lung disease (DPLD) as well as an atypical course of Epstein-Barr virus (EBV) infection. cord-290178-4i0z7ve8 2020 key: cord-290178-4i0z7ve8 title: Fatal SARS-CoV-2 coinfection in course of EBV-associated lymphoproliferative disease cord_uid: 4i0z7ve8 EBV belongs to the Herpesviridae family and causes infectious mononucleosis as well as chronic active infections; besides, it can induce various pre-cancerous or cancerous lymphoproliferative disorders, such as mucocutaneous ulcer, Hodgkin lymphoma, Burkitt lymphoma, diffuse large B cell lymphoma, plasmablastic lymphoma, plasma cell myeloma, angioimmunoblastic T cell lymphoma, follicular T cell lymphoma, extranodal NK/T cell lymphoma, and aggressive NK cell leukemia, particularly in immunodeficient and/or post-transplanted patients [3] . In these subjects, the synergic action of EBV and SARS-CoV-2 is assumed to be burden by a very high fatality rate. The chest X-ray performed at the patient''s bed in isolation hospital room shows a diffuse bilateral interstitial pneumonia (c) Clinical characteristics of 3,062 COVID-19 patients: a meta-analysis Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study cord-291063-de7v4e5s 2009 The expressions of EBV-encoded miRNAs in clinical samples and computational analysis to predict putative targets were applied to unravel the biological functions of EBV miRNAs. These approaches showed that the miR-BARTs are abundantly expressed in latently infected epithelial cells, nasopharyngeal carcinomas, EBV-associated gastric carcinoma cell lines and tissues, Burkitt''s lymphomas latency type I, EBV positive primary effusion lymphomas, and diffuse large B-cell lymphomas, but at a significantly lower level in B cells. However, computational alignment of the potential HIV-1 miRNAs with specific human T-cell mRNAs identified potential cellular targets including genes encoding CD4, CD28 and interleukin-2, IL-3, and IL-12 [119] . The idea of targeting viral transcripts is not new, and RNA interference has been demonstrated to efficiently mediate inhibition of replication of human pathogenic viruses such as HIV-1, HCV, dengue virus, severe acute respiratory syndrome (SARS) coronavirus, poliovirus, human rhinovirus, influenza A virus, hepatitis D virus, HBV, HSV-1, HPV, JCV, EBV, and CMV in cell culture (reviewed in [12] ). cord-291295-7og5umiq 2019 Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitin-specific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. Conversely, ectopic CYPA overexpression in the EBV-positive cell lines resulted in an increase in the EBNA1 expression levels detected by WB and qRT-PCR (Figures 3D,E) . EBNA1 protein expression was restored in the C2089-shCYPA cells transfected with the wild-type CYPA expression plasmid ( Figure 4B ). As shown in Figure 4D , CYPA interference (shCYPA) reduced the EBNA1 binding to oriP DNA by approximately 50% compared to that of the control (shNC) in HEK293 cells (P < 0.05). (F) CsA and elevated CYPA on EBNA1-oriP-mediated transcription activity in the luciferase reporter assay in HEK293 cells. cord-291481-ov1gkgpc 2016 In patients requiring mechanical ventilation, herpesviruses, mainly HSV1 and hCMV, may be frequently detected from either upper or lower respiratory tract Abstract Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. One hundred and eight clinical samples from upper and lower respiratory tract from the 54 ICU patients were analyzed to detect influenza and other respiratory viruses and a group of herpesviruses (EBV, hCMV and HSV1). This report concerns a group of 54 patients admitted to ICU because of ARDS with unknown causative agent; 19 of them were infected by influenza virus, as demonstrated by the detection of viral RNA in both upper and lower respiratory tract samples. cord-297222-2danzbqt 2020 Hemophagocytic lymphohistiocytosis (HLH) is an immune related clinical syndrome with protean manifestations, varying presentation, clinically complex, with diverse causes, and is an under-recognized entity which carries high morbidity and mortality. Hemophagocytic lymphohistiocytosis (HLH) is an extremely rare and potentially lifethreatening hematological disorder, characterized by clinical features of extreme inflammation and an unregulated immune system. We describe a case of Epstein-Barr virus (EBV)-associated HLH with its typical diagnostic challenges and associated high mortality rate, but an early prompt diagnosis with appropriate treatment can lead to better outcomes. The major finding in the patient''s autopsy was hemophagocytic histiocytosis with rare EBVpositivity noted in the bone marrow analysis, suggesting that the HLH was due to EBV infection. The official cause of death in the patient was determined to be pulmonary aspergillosis with organizing pneumonia in the setting of hemophagocytic lymphohistiocytosis, likely secondary to Epstein-Barr virus infection. cord-304986-lk2ikxda 2016 cord-305746-svg3h2oi 2017 cord-307016-4hdsb5oq 2010 cord-323854-l8gfr19i 2018 cord-327883-s9nbr5y8 1990 By improving the enzyme-linked immunosorbent assay (ELISA) for HSV-2-antibodies and additional testing of sera by Western blot, we were able to specifically identify HSV-l-and HSV-2-antibodies in serum samples. To get some insight into the molecular basis of processes controlling the viral expression we studied the sequence-specific DNA-protein interactions within the genomic regulatory regions. for Med. Microbiology, Univ., D-5300 Bonn Semiquantitative detection of Hepatitis B Virus (HBV) DNA in sera of infected individuals has become an important means of modern serological hepatitis diagnostics. THOMSSEN 1 In the course of acute Epstein-Barr virus (EBV) infection IgM antibodies always occur against two cellular antigens that were characterized as proteins with a molecular weight of 26 kD (p26) and 29 kD (p29), respectively. The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). cord-328647-0dut550o 2007 cord-330698-9t24jo8s 2012 Finally, endogenous retrovirus and retrotransposon elements deposited in our genomes millions of years ago can be released from cells within microvesicles, suggestive of a viral origin of the microvesicle system or perhaps of an evolutionary conserved system of virus-vesicle codependence. Microvesicles released by infected cells contain specific components of the cell and the virus, many of which facilitate the ability of virions to persist in a hostile antiviral immune environment [44, 55, 56, 58] . During HSV-1 infection the release of microvesicles, formerly known as L-particles containing viral tegument proteins and glycoproteins, can prime surrounding cells for productive infection and reduce immune rejection [48] [49] [50] . In the case of the human CMV, microvesicles released by infected cells present the C-type lectin family molecule expressed on dendritic cells-used in capture and internalization of pathogens-in complex with the CMV glycoprotein B. Also, the convergence of these pathways may explain the observations of virus-like particles, which can be exosomes or shed microvesicles containing viral proteins or nucleic acids. cord-340228-mvqoyror 2019 Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The distribution of these patients according to PID categories is: immunodeficiencies affecting cellular and humoral immunity, 97 patients (35.4%); combined immunodeficiencies with associated syndromic features, 67 patients (24.5%); predominantly antibody deficiencies, 34 patients (12.4%); diseases of immune dysregulation, 47 patients (17.2%); congenital defects of phagocyte number or function, 17 patients (6.2%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 11 patients (4%). cord-341106-algs6573 2009 cord-342054-1u2fkwx3 2008 The available therapeutic armamentarium (e.g. HCMV hyperimmune globulins or antivirals) is associated with severe side effects and the emergence of drug-resistant strains; therefore, neutralizing human mAb may be a decisive alternative in the prevention of primary and re-activated HCMV infections in these patients. The strengths of this approach are: i) it allows the selection of human monoclonal IgG to a variety of antigens, from a small sample of fresh or frozen peripheral blood, ii) it is rapid, iii) screening can be performed using a variety of assays, including functional assays, iv) the mAbs of interest can be easily produced from the original clone as recombinant proteins suitable for clinical applications, and v) the generation of IgGsecreting polyclonal populations can be considered as a library of antibody-secreting cells that can be used to select mAbs with specificities not considered when cells were immortalized. cord-345922-3waid65i 2018 Inset shows the ratio between genders and that women are twice as likely than men to develop MS Significance Despite major research efforts in the past few decades, the extent to which environmental factors (including external pathogens) and genetic susceptibility contribute to the pathogenesis of multiple sclerosis (MS) is not clearly identified. Even though different animal models of MS, such as the experimental autoimmune encephalitis (EAE) model and TMEV model aided in the understanding of possible underlying mechanisms including molecular mimicry and bystander activation, animal models for the most commonly associated viruses HHV-6 and EBV have yet to be developed (Virtanen & Jacobson, 2012) . B cell immunity plays an integral part in the development of MS because of its role in antibody presentation, cytokine production, meningeal inflammation, axonal degeneration, and grey matter F I G U R E 3 Schematic diagram of environmental factors and host derived pathways in causation of the disease and therapeutic strategies associated with multiple sclerosis (MS) progression. cord-348388-nkosag8m 2020 cord-350807-qdq96723 2020 cord-356062-7q5n4t97 2005