BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric can...BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.展开更多
Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly...Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly affecting the liver. Diagnosis relies on a combination of clinical presentation and laboratory parameters, with commonly used indicators including EBV-specific antibodies, EBV-DNA load, and the ratio of atypical lymphocytes. Treatment primarily involves symptomatic supportive care, with a cautious approach to the routine use of antiviral medications. In recent years, significant research in traditional Chinese medicine has been conducted in China, showing promising advancements. This article provides a comprehensive review of EBV-induced infectious mononucleosis, offering insights for clinical diagnosis and treatment.展开更多
BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate...BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.展开更多
BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a severe hyperinflammatory reaction,which is rare and life-threatening.According to the pathogen,HLH is divided into genetic and acquired.The most common form of ac...BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a severe hyperinflammatory reaction,which is rare and life-threatening.According to the pathogen,HLH is divided into genetic and acquired.The most common form of acquired HLH is infection-associated HLH,of which Herpes viruses,particularly Epstein-Barr virus(EBV),are the leading infectious triggers.However,it is difficult to distinguish between simple infection with EBV and EBV-induced infectionassociated HLH since both can destroy the whole-body system,particularly the liver,thereby increasing the difficulty of diagnosis and treatment.CASE SUMMARY This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury,aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH.The patient was categorized as acquired hemophagocytic syndrome in adults.After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response,gamma globulin enhanced immunotherapy,the patient recovered.CONCLUSION From the diagnosis and treatment of this patient,attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients’survival.展开更多
The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis duri...The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.展开更多
AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective...AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by immunohistochemistry.RESULTS The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.展开更多
Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)i...Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.展开更多
BACKGROUND Epstein-Barr virus associated smooth muscle tumor(EBV-SMT)is a rare oncological entity.However,there is an increasing incidence of EBV-SMTs,as the frequency of organ transplantation and immunosuppression gr...BACKGROUND Epstein-Barr virus associated smooth muscle tumor(EBV-SMT)is a rare oncological entity.However,there is an increasing incidence of EBV-SMTs,as the frequency of organ transplantation and immunosuppression grows.EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder(PTLD).There is no clear consensus on the treatment of EBV-SMTs.However,surgical resection,chemotherapy,radiation therapy,and immunosuppression reduction have been explored with varying degrees of success.CASE SUMMARY Our case series includes six cases of EBV-SMTs across different age groups,with different treatment modalities,adding to the limited existing literature on this rare tumor.The median latency time between immunosuppression and disease diagnosis is four years.EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency.CONCLUSION It is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.展开更多
BACKGROUND The diagnosis and etiology of multiple primary malignant neoplasms(MPMNs)are difficult to establish.Here,we report a case of heterochronic triple primary malignancies with gastric cancer,nasopharyngeal squa...BACKGROUND The diagnosis and etiology of multiple primary malignant neoplasms(MPMNs)are difficult to establish.Here,we report a case of heterochronic triple primary malignancies with gastric cancer,nasopharyngeal squamous cell cancer,and then rectal cancer.CASE SUMMARY The patient was first diagnosed with gastric cancer at the age of 33 in 2014 and underwent distal gastrectomy and gastrojejunostomy and six cycles of adjuvant chemotherapy.Three years later,he was diagnosed with nasopharyngeal cancer and treated with radical chemoradiotherapy in 2017.Recently,a mass in the middle of the rectum was resected and reported as ulcerative,moderately to poorly differentiated adenocarcinoma.Research on the etiology of MPMNs showed that Epstein-Barr virus(EBV)infection may be the cause of gastric cancer and nasopharyngeal squamous cell cancer since these two primary lesions were positive for transcripts of EBV-encoded ribonucleic acid using an in situ hybridization EBV-encoded ribonucleic acid probe in formalin-fixed,paraffinembedded tissue.The cause of rectal cancer may be due to a somatic mutation of tumor protein 53 gene in exon 8(c.844C>T,p.Arg282Trp)through highthroughput sequencing for the rectal cancer.Appropriate standard therapy for each primary cancer was administered,and the patient has no evidence of cancer disease to date.CONCLUSION To our knowledge,this is the first report on heterochronic triple primary malignancies whose cause may be associated with EBV infection and tumor protein 53 genetic mutations.The etiological research may not only elucidate the cause of MPMN but also has implications in clinical management.展开更多
AIM: To investigate the positive rate and types of cells that express Epstein-Barr virus-encoded small RNAs (EBERs) and to determine the distribution of EBER-expressing cells in idiopathic orbital inflammatory pseu...AIM: To investigate the positive rate and types of cells that express Epstein-Barr virus-encoded small RNAs (EBERs) and to determine the distribution of EBER-expressing cells in idiopathic orbital inflammatory pseudotumor (IOIP) tissues. METHODS: We retrospectively examined 40 archived paraffin specimens from two teaching hospitals in Southern China between January 2007 and January 2015 that were pathologically determined to exhibit IOIP. Eleven concurrent paraffin specimens of thyroid-associated ophthalmopathy (TAO) composed the control group. In situ hybridization was performed to detect EBERs. Immunohistochemistry was employed to detect CD3, CD20, Vimentin, and smooth muscle actin (SMA), and the positive rate, types of positive cells, and distribution and location of EBERs were evaluated. RESULTS: The positive expression rate of EBERs was 47.5% (19/40) in the IOIP group, which was significantly higher than that in the TAO group [0 (0/11), P=-0.011]. in the IOIP group, the lymphocyte infiltrative subtype, fibrotic subtype, and mixed subtype exhibited EBER-positive rates of 57.1% (12121), 12.5% (118), and 54.5% (6/11), respectively, and no significant differences were found between these subtypes (P=0.085). Positive signals of EBERs were mainly present in medium-small lymphocytes between or around follicles and in the nuclei of activated immunoblasts (14/19). CONCLUSION: The positive rate, types, and distribution of EBER-expressing cells in IOIP have been documented.These findings are conducive for a better understanding of the underlying mechanisms of Epstein-Barr virus infection in IOIP pathogenesis.展开更多
The study investigated the distribution of Epstein-Barr virus(EBV)EA-IgA,VCAIgA,and EBVNA-IgG antibodies in a local population of Wuhan,China.Chemiluminescence immunoassay(CL1A)was used to detect EBV EA-IgA,VCA-IgA,an...The study investigated the distribution of Epstein-Barr virus(EBV)EA-IgA,VCAIgA,and EBVNA-IgG antibodies in a local population of Wuhan,China.Chemiluminescence immunoassay(CL1A)was used to detect EBV EA-IgA,VCA-IgA,and EBVNA-IgG antibodies in 972 subjects undergoing physical examination in Wuhan,and the results were analyzed.The detection rate of EBV was positively correlated with age.In the 972 cases,there was significant difference between different genders in the positive rate of VCA-IgA and EBVNA-IgG.Moreover,the positive rate of VCA-IgA and EBVNA-IgG was higher in men>60 years old than in those<60 but no significant differences were found in three antibodies among various age groups.Our results suggested that the EBV infection should be intensively monitored in elderly people in Wuhan.展开更多
Ether extrilcls of 1693 Chinesc medicinal herbs and plilnts from 268 families werestudied for the induction of Epstcin-Barr viral (EBV ) early antigcn (EA ) expression in theRaji cell line. Fifty-two from 18 families ...Ether extrilcls of 1693 Chinesc medicinal herbs and plilnts from 268 families werestudied for the induction of Epstcin-Barr viral (EBV ) early antigcn (EA ) expression in theRaji cell line. Fifty-two from 18 families were found to have inducing activity. Twenty-fiveand seven of them were from Euphorbiaccae and Thymclaeaceae, respectively. Some ofthem, such as Croton tiglium, Euphorbia kansui, Daphnc genkwa, Wikstrocmia chamacdaphen, Wikstroemia indica, Prunus mandshurica Koehne and Achyranthes bidentata arecommonly used drugs. The significance of these herbs in the activation of EBV in vivo andtheir relation to the development of nasopharyngeal carcinoma were discussed.展开更多
BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV...BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV(CAEBV),and hematopoietic stem cell transplantation is the only effective treatment.We here report a CAEBV patient treated with PEG-aspargase,who achieved negative EBV-DNA.CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017.EBV-DNA was positive with a high copy number.She was diagnosed with chronic active EB virus infection.PEGaspargase was administered at a dose of 1500 U/m2 at a 14-d interval,resulting in eradication of EBV for more than 6 mo.The effect of PEG-aspargase in this patient was excellent.CONCLUSION A chemotherapy regimen containing PEG-aspargase for CAEBV may be further considered.展开更多
BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The c...BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD.CASE SUMMARY We report two Epstein-Barr virus(EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD.CONCLUSION PTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.展开更多
Objective: This study aimed to comprehensively assess Epstein-Barr virus(EBV)-induced methylation alterations of B cell across whole genome.Methods: We compared DNA methylation patterns of primary B cells and corr...Objective: This study aimed to comprehensively assess Epstein-Barr virus(EBV)-induced methylation alterations of B cell across whole genome.Methods: We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines(LCLs) from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results: DNA methylation analysis revealed 87,732 differentially methylated Cp G sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated Cp G sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in Cp G islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore(N_shore and S_shore). Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions: Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.展开更多
We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine ...We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. Given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout.展开更多
Objective:Circulating cell-free Epstein-Barr virus(EBV)DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma(NPC).Despite important insights in...Objective:Circulating cell-free Epstein-Barr virus(EBV)DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma(NPC).Despite important insights into the biology of persistence,few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells(PBCs).Methods:A prospective observational cohort study was conducted involving 1,063 newly diagnosed,locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007.Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival(OS)and other prognostic outcomes.Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.Results:After a median follow-up of 108 months,patients with higher PBC EBV-DNA loads had significantly worse OS[hazard ratio(HR)of medium,medium-high,and high vs.low were 1.50,1.52,and 1.85 respectively;Ptrend<0.001].Similar results were found for progression-free survival and distant metastasis-free survival.The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66,respectively.Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker,which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort(HR:1.88;P=0.025).Importantly,a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.Conclusions:The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.展开更多
Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids...Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain.The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses(herpes simplex virus 1,herpes simplex virus 2,varicella zoster virus,human cytomegalovirus,human herpesvirus 6,and human herpesvirus 7).From May 2019 to September 2020,64 serum samples of children following HSCT were collected.EBV infection and the viral load of serum samples were detected by cdPCR.The epidemiological characteristics of EBV infections were analyzed in HSCT patients.Results The limit of detection of EBV cdPCR was 110 copies/mL,and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid.The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain,and both were more sensitive than that of quantitative PCR.Using cdPCR,the incidence of EBV infection was 18.75%in 64 children after HSCT.The minimum EBV viral load was 140 copies/mL,and the maximum viral load was 3,209 copies/mL using cdPCR.The average hospital stay of children with EBV infection(184±91 days)was longer than that of children without EBV infection(125±79 days),P=0.026.Conclusion EBV cdPCR had good sensitivity and specificity.The incidence of EBV infection was 18.75%in 64 children after HSCT from May 2019 to September 2020.EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.展开更多
The Epstein-Barr virus membrane antigen was constructed and inserted into vaccinia virus, Tian-tan strain in order to study the effect of this virus on EB infection and tumorogenesis. The EBV-derived membrane antigen ...The Epstein-Barr virus membrane antigen was constructed and inserted into vaccinia virus, Tian-tan strain in order to study the effect of this virus on EB infection and tumorogenesis. The EBV-derived membrane antigen was expressed under the control of a 7.5 K promoter of vaccinia virus. The antibody against the membrane antigen of EB virus was produced on rabbits vaccinated with recombinant vaccinia virus.展开更多
BACKGROUND Primary non-Hodgkin’s lymphoma of the frontal sinus is extremely rare.In addition,Epstein-Barr virus(EBV)has been reported to play a role in the development of human immunodeficiency virus(HIV)-related mal...BACKGROUND Primary non-Hodgkin’s lymphoma of the frontal sinus is extremely rare.In addition,Epstein-Barr virus(EBV)has been reported to play a role in the development of human immunodeficiency virus(HIV)-related malignant lymphomas.To the best of our knowledge,there is no report for the HIVassociated,EBV-positive primary diffuse large B-cell lymphoma(DLBCL)in the frontal sinus.CASE SUMMARY We present a unique case of HIV-associated,EBV-positive DLBCL in the frontal sinus in a 46-year-old man.Computed tomography of paranasal sinuses revealed dense opacification of the right frontal sinus with combined soft tissue swelling.Based on the clinical and radiological findings,the initial diagnosis was complicated frontal sinusitis,presenting Pott’s puffy tumor.Unexpectedly,HIV testing was positive on preoperative laboratory test,and the frontal sinus lesion was confirmed as EBV-positive DLBCL on biopsy.CONCLUSION Through this article,we suggest that EBV-positive DLBCL should be considered as possible diagnosis for patients with nonspecific space-occupying lesion of the paranasal sinuses.We also highlight an importance of clinical suspicion in diagnosing HIV infection because HIV serology is not routinely tested in patients with paranasal sinus problem.展开更多
基金Supported by the Sub-Project of the National Key Research and Development Program,No.2021YFC2600263.
文摘BACKGROUND N6-methyladenosine(m6A)methylation modification exists in Epstein-Barr virus(EBV)primary infection,latency,and lytic reactivation.It also modifies EBV latent genes and lytic genes.EBV-associated gastric cancer(EBVaGC)is a distinctive molecular subtype of GC.We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC.AIM To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC.METHODS First,The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC(EBVnGC).Second,we identified Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment of m6A-related differentially expressed genes.We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment(TME).Finally,cell counting kit-8 cell proliferation test,transwell test,and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1(IGFBP1)in EBVaGC cell lines.RESULTS m6A methylation regulators were involved in the occurrence and development of EBVaGC.Compared with EBVnGC,the expression levels of m6A methylation regulators Wilms tumor 1-associated protein,RNA binding motif protein 15B,CBL proto-oncogene like 1,leucine rich pentatricopeptide repeat containing,heterogeneous nuclear ribonucleoprotein A2B1,IGFBP1,and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC(P<0.05).The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher(P=0.046).GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC.Compared with EBVnGC,the infiltration of activated CD4+T cells,activated CD8+T cells,monocytes,activated dendritic cells,and plasmacytoid dendritic cells were significantly upregulated in EBVaGC(P<0.001).In EBVaGC,the expression level of proinflammatory factors interleukin(IL)-17,IL-21,and interferon-γ and immunosuppressive factor IL-10 were significantly increased(P<0.05).In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line(SNU719)than in an EBVnGC cell line(AGS)(P<0.05).IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719.Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS.CONCLUSION m6A regulators could remodel the TME of EBVaGC,which is classified as an immune-inflamed phenotype and referred to as a“hot”tumor.Among these regulators,we demonstrated that IGFBP1 affected proliferation,migration,and apoptosis.
文摘Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly affecting the liver. Diagnosis relies on a combination of clinical presentation and laboratory parameters, with commonly used indicators including EBV-specific antibodies, EBV-DNA load, and the ratio of atypical lymphocytes. Treatment primarily involves symptomatic supportive care, with a cautious approach to the routine use of antiviral medications. In recent years, significant research in traditional Chinese medicine has been conducted in China, showing promising advancements. This article provides a comprehensive review of EBV-induced infectious mononucleosis, offering insights for clinical diagnosis and treatment.
基金Supported by Clinical and Translational Medicine Research Foundation of Chinese Academy of Medical Sciences,No. 2020-I2M-C&T-B-038Capital Health Research and Development of Special Project,No. 2022-1-2181Group Medical Aid Project of the Tibet Autonomous Region Natural Science Foundation,No. XZ2020ZR-ZY28[Z]
文摘BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.
基金Supported by the National Natural Science Foundation of China,No.82174189Talents Training Program of Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine,No.JCR2022-01+3 种基金TCM Specialist Disease Alliance Construction Project of Shanghai Municipal Health Commission,No.ZY(2021-2023)-0302Talent Training Project of Senior Master of Chinese Medicine of Shanghai Pudong,No.PDZY-2022-0601Project of Introducing Senior Talents of Chinese Medicine of Shanghai Pudong,No.PDZY-2022-0701Talents Training Program of the Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine,No.QMX2021-04.
文摘BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a severe hyperinflammatory reaction,which is rare and life-threatening.According to the pathogen,HLH is divided into genetic and acquired.The most common form of acquired HLH is infection-associated HLH,of which Herpes viruses,particularly Epstein-Barr virus(EBV),are the leading infectious triggers.However,it is difficult to distinguish between simple infection with EBV and EBV-induced infectionassociated HLH since both can destroy the whole-body system,particularly the liver,thereby increasing the difficulty of diagnosis and treatment.CASE SUMMARY This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury,aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH.The patient was categorized as acquired hemophagocytic syndrome in adults.After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response,gamma globulin enhanced immunotherapy,the patient recovered.CONCLUSION From the diagnosis and treatment of this patient,attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients’survival.
文摘The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.
基金supported by FEDER through the operation POCI-01-0145-FEDER-007746 funded by the Programa Operacional Competitividade e Internacionalizacao–COMPETE2020by National Funds through FCT-Fundacao para a Ciencia e a Tecnologia within CINTESIS,R&D Unit(reference UID/IC/4255/2013)Joana Ribeiro has been granted with a Ph D Scholarship(SFRH/BD/107740/2015)from FCT-Fundacao para Ciencia e Tecnologia
文摘AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by immunohistochemistry.RESULTS The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.
基金Supported by Grant-in-Aid for Scientific Research From the Ministry of Education,Culture,Science and Technology of Japan,No.21K07054(Hironori Yoshiyama)and No.22K07101(Hisashi Iizasa).
文摘Epstein-Barr virus(EBV)-associated gastric cancer(EBVaGC)cells originate from a single-cell clone infected with EBV.However,more than 95%of patients with gastric cancer have a history of Helicobacter pylori(H.pylori)infection,and H.pylori is a major causative agent of gastric cancer.Therefore,it has long been argued that H.pylori infection may affect the development of EBVaGC,a subtype of gastric cancer.Atrophic gastrointestinal inflammation,a symptom of H.pylori infection,is observed in the gastric mucosa of EBVaGC.Therefore,it remains unclear whether H.pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H.pylori and EBV infections act independently on gastric cancer formation.It has been reported that EBV infection assists in the oncogenesis of gastric cancer caused by H.pylori infection.In contrast,several studies have reported that H.pylori infection accelerates tumorigenesis initiated by EBV infection.By reviewing both clinical epidemiological and experimental data,we reorganized the role of H.pylori and EBV infections in gastric cancer formation.
文摘BACKGROUND Epstein-Barr virus associated smooth muscle tumor(EBV-SMT)is a rare oncological entity.However,there is an increasing incidence of EBV-SMTs,as the frequency of organ transplantation and immunosuppression grows.EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder(PTLD).There is no clear consensus on the treatment of EBV-SMTs.However,surgical resection,chemotherapy,radiation therapy,and immunosuppression reduction have been explored with varying degrees of success.CASE SUMMARY Our case series includes six cases of EBV-SMTs across different age groups,with different treatment modalities,adding to the limited existing literature on this rare tumor.The median latency time between immunosuppression and disease diagnosis is four years.EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency.CONCLUSION It is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.
文摘BACKGROUND The diagnosis and etiology of multiple primary malignant neoplasms(MPMNs)are difficult to establish.Here,we report a case of heterochronic triple primary malignancies with gastric cancer,nasopharyngeal squamous cell cancer,and then rectal cancer.CASE SUMMARY The patient was first diagnosed with gastric cancer at the age of 33 in 2014 and underwent distal gastrectomy and gastrojejunostomy and six cycles of adjuvant chemotherapy.Three years later,he was diagnosed with nasopharyngeal cancer and treated with radical chemoradiotherapy in 2017.Recently,a mass in the middle of the rectum was resected and reported as ulcerative,moderately to poorly differentiated adenocarcinoma.Research on the etiology of MPMNs showed that Epstein-Barr virus(EBV)infection may be the cause of gastric cancer and nasopharyngeal squamous cell cancer since these two primary lesions were positive for transcripts of EBV-encoded ribonucleic acid using an in situ hybridization EBV-encoded ribonucleic acid probe in formalin-fixed,paraffinembedded tissue.The cause of rectal cancer may be due to a somatic mutation of tumor protein 53 gene in exon 8(c.844C>T,p.Arg282Trp)through highthroughput sequencing for the rectal cancer.Appropriate standard therapy for each primary cancer was administered,and the patient has no evidence of cancer disease to date.CONCLUSION To our knowledge,this is the first report on heterochronic triple primary malignancies whose cause may be associated with EBV infection and tumor protein 53 genetic mutations.The etiological research may not only elucidate the cause of MPMN but also has implications in clinical management.
基金Supported by the National Natural Science Foundation of China(No.81260149No.81360152+2 种基金No.81560162)Guangxi Natural Science Foundation(No.2016GXNSFAA380301)Youth Science Foundation of Guangxi Medical University(No.GXMUYSF2014040)
文摘AIM: To investigate the positive rate and types of cells that express Epstein-Barr virus-encoded small RNAs (EBERs) and to determine the distribution of EBER-expressing cells in idiopathic orbital inflammatory pseudotumor (IOIP) tissues. METHODS: We retrospectively examined 40 archived paraffin specimens from two teaching hospitals in Southern China between January 2007 and January 2015 that were pathologically determined to exhibit IOIP. Eleven concurrent paraffin specimens of thyroid-associated ophthalmopathy (TAO) composed the control group. In situ hybridization was performed to detect EBERs. Immunohistochemistry was employed to detect CD3, CD20, Vimentin, and smooth muscle actin (SMA), and the positive rate, types of positive cells, and distribution and location of EBERs were evaluated. RESULTS: The positive expression rate of EBERs was 47.5% (19/40) in the IOIP group, which was significantly higher than that in the TAO group [0 (0/11), P=-0.011]. in the IOIP group, the lymphocyte infiltrative subtype, fibrotic subtype, and mixed subtype exhibited EBER-positive rates of 57.1% (12121), 12.5% (118), and 54.5% (6/11), respectively, and no significant differences were found between these subtypes (P=0.085). Positive signals of EBERs were mainly present in medium-small lymphocytes between or around follicles and in the nuclei of activated immunoblasts (14/19). CONCLUSION: The positive rate, types, and distribution of EBER-expressing cells in IOIP have been documented.These findings are conducive for a better understanding of the underlying mechanisms of Epstein-Barr virus infection in IOIP pathogenesis.
基金grants from the Natural Science Foundation of Hubei Province(No.2018CFB749 and No.2018ADC073)the Scientific Research Fund of Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(No.02.03.2017-292 and No.02.03.2017-327)General Project of Hubei Health Committee(No.02.07.19030018).
文摘The study investigated the distribution of Epstein-Barr virus(EBV)EA-IgA,VCAIgA,and EBVNA-IgG antibodies in a local population of Wuhan,China.Chemiluminescence immunoassay(CL1A)was used to detect EBV EA-IgA,VCA-IgA,and EBVNA-IgG antibodies in 972 subjects undergoing physical examination in Wuhan,and the results were analyzed.The detection rate of EBV was positively correlated with age.In the 972 cases,there was significant difference between different genders in the positive rate of VCA-IgA and EBVNA-IgG.Moreover,the positive rate of VCA-IgA and EBVNA-IgG was higher in men>60 years old than in those<60 but no significant differences were found in three antibodies among various age groups.Our results suggested that the EBV infection should be intensively monitored in elderly people in Wuhan.
文摘Ether extrilcls of 1693 Chinesc medicinal herbs and plilnts from 268 families werestudied for the induction of Epstcin-Barr viral (EBV ) early antigcn (EA ) expression in theRaji cell line. Fifty-two from 18 families were found to have inducing activity. Twenty-fiveand seven of them were from Euphorbiaccae and Thymclaeaceae, respectively. Some ofthem, such as Croton tiglium, Euphorbia kansui, Daphnc genkwa, Wikstrocmia chamacdaphen, Wikstroemia indica, Prunus mandshurica Koehne and Achyranthes bidentata arecommonly used drugs. The significance of these herbs in the activation of EBV in vivo andtheir relation to the development of nasopharyngeal carcinoma were discussed.
基金Supported by National Natural Science Foundation of China,No.81871633Beijing Natural Science Foundation,No.7181003Beijing Municipal Administration of Hospitals’Ascent Plan,No.DFL20180101.
文摘BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV(CAEBV),and hematopoietic stem cell transplantation is the only effective treatment.We here report a CAEBV patient treated with PEG-aspargase,who achieved negative EBV-DNA.CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017.EBV-DNA was positive with a high copy number.She was diagnosed with chronic active EB virus infection.PEGaspargase was administered at a dose of 1500 U/m2 at a 14-d interval,resulting in eradication of EBV for more than 6 mo.The effect of PEG-aspargase in this patient was excellent.CONCLUSION A chemotherapy regimen containing PEG-aspargase for CAEBV may be further considered.
基金Supported by the National Natural Science Foundation of China,No.81771720
文摘BACKGROUND Post-transplant lymphoproliferative disorder(PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD.CASE SUMMARY We report two Epstein-Barr virus(EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD.CONCLUSION PTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.
基金supported by grants from National Natural Science Foundation of China (No. 81160249, 81301886 and 81760525)Science Foundation of Peking University Cancer Hospital (No. 2017 Zizhu-1)+4 种基金Open Project funded by Key Laboratory of Carcinogenesis and Translational ResearchMinistry of Education/Beijing (2017 Open Project-3)Beijing Municipal Science & Technology Commission (No. Z171100001017136)Beijing Natural Science Foundation (No. 7171001)West China First-Class Discipline Construction Project in Basic Medicine funded by Ningxia Medical University
文摘Objective: This study aimed to comprehensively assess Epstein-Barr virus(EBV)-induced methylation alterations of B cell across whole genome.Methods: We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines(LCLs) from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results: DNA methylation analysis revealed 87,732 differentially methylated Cp G sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated Cp G sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in Cp G islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore(N_shore and S_shore). Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions: Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.
文摘We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. Given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2016YFC0902001)the Sino-Sweden Joint Research Program(Grant No.81861138006)+5 种基金the Science and Technology Planning Project of Guangzhou,China(Grant No.201804020094)the National Natural Science Foundation of China(Grant Nos.81973131,81903395,81803319,and 81502056)the National Science Fund for Distinguished Young Scholars of China(Grant No.81325018)the Key Project for International Cooperation and Exchange of the National Natural Science Foundation of China(Grant No.81220108022)the Natural Science Foundation of Guangdong Province(Grant No.2017A030312003)。
文摘Objective:Circulating cell-free Epstein-Barr virus(EBV)DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma(NPC).Despite important insights into the biology of persistence,few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells(PBCs).Methods:A prospective observational cohort study was conducted involving 1,063 newly diagnosed,locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007.Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival(OS)and other prognostic outcomes.Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.Results:After a median follow-up of 108 months,patients with higher PBC EBV-DNA loads had significantly worse OS[hazard ratio(HR)of medium,medium-high,and high vs.low were 1.50,1.52,and 1.85 respectively;Ptrend<0.001].Similar results were found for progression-free survival and distant metastasis-free survival.The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66,respectively.Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker,which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort(HR:1.88;P=0.025).Importantly,a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.Conclusions:The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.
基金supported by the Research Project Supported by the China Mega-Project for Infectious Disease[2018ZX10102001,2018ZX10711001,and 2018ZX10734404]National Pathogen Resource Collection Center[NPRC-32]the SKLID Development Grant[2011SKLID104]。
文摘Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain.The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses(herpes simplex virus 1,herpes simplex virus 2,varicella zoster virus,human cytomegalovirus,human herpesvirus 6,and human herpesvirus 7).From May 2019 to September 2020,64 serum samples of children following HSCT were collected.EBV infection and the viral load of serum samples were detected by cdPCR.The epidemiological characteristics of EBV infections were analyzed in HSCT patients.Results The limit of detection of EBV cdPCR was 110 copies/mL,and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid.The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain,and both were more sensitive than that of quantitative PCR.Using cdPCR,the incidence of EBV infection was 18.75%in 64 children after HSCT.The minimum EBV viral load was 140 copies/mL,and the maximum viral load was 3,209 copies/mL using cdPCR.The average hospital stay of children with EBV infection(184±91 days)was longer than that of children without EBV infection(125±79 days),P=0.026.Conclusion EBV cdPCR had good sensitivity and specificity.The incidence of EBV infection was 18.75%in 64 children after HSCT from May 2019 to September 2020.EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.
文摘The Epstein-Barr virus membrane antigen was constructed and inserted into vaccinia virus, Tian-tan strain in order to study the effect of this virus on EB infection and tumorogenesis. The EBV-derived membrane antigen was expressed under the control of a 7.5 K promoter of vaccinia virus. The antibody against the membrane antigen of EB virus was produced on rabbits vaccinated with recombinant vaccinia virus.
文摘BACKGROUND Primary non-Hodgkin’s lymphoma of the frontal sinus is extremely rare.In addition,Epstein-Barr virus(EBV)has been reported to play a role in the development of human immunodeficiency virus(HIV)-related malignant lymphomas.To the best of our knowledge,there is no report for the HIVassociated,EBV-positive primary diffuse large B-cell lymphoma(DLBCL)in the frontal sinus.CASE SUMMARY We present a unique case of HIV-associated,EBV-positive DLBCL in the frontal sinus in a 46-year-old man.Computed tomography of paranasal sinuses revealed dense opacification of the right frontal sinus with combined soft tissue swelling.Based on the clinical and radiological findings,the initial diagnosis was complicated frontal sinusitis,presenting Pott’s puffy tumor.Unexpectedly,HIV testing was positive on preoperative laboratory test,and the frontal sinus lesion was confirmed as EBV-positive DLBCL on biopsy.CONCLUSION Through this article,we suggest that EBV-positive DLBCL should be considered as possible diagnosis for patients with nonspecific space-occupying lesion of the paranasal sinuses.We also highlight an importance of clinical suspicion in diagnosing HIV infection because HIV serology is not routinely tested in patients with paranasal sinus problem.