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 Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or agin...BACKGROUND Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression.The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas.We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU.Through this case,we aim to emphasize the importance of accurately distinguishing between the two conditions.CASE SUMMARY The patient presented with an incidental finding of a small bowel tumor during computed tomography(CT)examination performed for hematuria.The CT scan showed irregular thickening of the distal ileum,which was suggestive of a malignant small bowel tumor.An exploratory laparotomy revealed an 8-cm mass in the distal ileum;thus,a segment of the small intestine,including the mass,was resected.Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing,marked inflammatory cell infiltration,and large atypical lymphoid cells(positive for EBV-encoded small RNA).A final diagnosis of an EBV-MCU was established.The postoperative course was uneventful,and the patient was discharged on postoperative day 7.The patient remained recurrencefree until 12 mo after surgery.CONCLUSION This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.展开更多
This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previously reported to be associated with EBV. These studies showed that J6-1 cells were also infected with...This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previously reported to be associated with EBV. These studies showed that J6-1 cells were also infected with HHV-6 as demonstrate at the DNA level by PCR and Southern blot hybridization and by expression of HHV-6 early membrane antigen on the J6-1 cell surface. Further characterization showed J6-1 was co-infected with EBV type 2. Generally, cells infected with EBV type 2 do not grow well in vitro. However, J6-1 , although difficult to maintain in vitro, has been grown for 15 years. Possibly, co-infection with HHV6 confers this property. In this regard, J6-1 cells exhibited density dependent growth which could be inhibited with an anti-HHV-6-MA monoclonal antibody(MAb). In contrast, anti-HHV-6-VCA MAb stimulated the J6-1 cell proliferation. Electron microscopic analysis showed that, morphologically, there were two types of J6-1 cell, one with lymphoblastoid features and one with a monocytoid appearance. Accordingly, the flow profile of the J6-1 cell line showed heterogeneity. with two populations comprised of CD15-, CD19+ cells with low light scatter(small cells) and a population with greater light scatter(larger cells) which was CD15+ , CD19+. The population was negative for progenitor cell markers(CD33, 34 ), and T cell markers. Southern analysis showed no T cell receptor rearrangement, however there was a clonal JH and kappa light chain expressing population. Glycocytochemical analysis showed several endogenous lectin receptors on the J6-1 cell surface: BSA-Xylose, BSA-Rhamnose, BSAGal. BSA-Lac. This cell line shares many characteristics with other monocytic/ lymphoblastoid cell lines isolated elsewhere and provides circumstantial evidence linking Herpes viruses, as least as co- factors,to leukemia cell growth.展开更多
In order to explore the relationship between Epstein Barr virus (EBV) and pathogenesis of multiple myeloma (MM), the presence of EBV DNA in mononuclear cells of bone marrow (BMMC) and peripheral blood (PBMC) taken f...In order to explore the relationship between Epstein Barr virus (EBV) and pathogenesis of multiple myeloma (MM), the presence of EBV DNA in mononuclear cells of bone marrow (BMMC) and peripheral blood (PBMC) taken from 23 multiple myeloma patients who were neither posttransplanted nor HIV positive were examined by polymerase chain reaction (PCR). Meanwhile the presence of EBV EBERs in bioptic bone marrow's specimens of 4 MM patients were examined by in situ hybridization (ISH). Acute leukemia, aplastic anemia and malnourished anemia patients were taken as control. It showed EBV DNA detective rate in BMMC (69 6%) and in PBMC (39 1%) of MM patients were higher significantly than control groups (P<0 05). The positive signals of EBERs were located in BMMC and the EBV positive samples detected by ISH were consistent with those by PCR. The results indicate that EBV is closely correlated to pathogenesis of MM.展开更多
In 1987, a mass survey of EDAb was carried out in Sihui county of Gunagdong Province (the highest incidence area of NPC in China) and the city of Guangzhou using the methods previously established by our lab. In orde...In 1987, a mass survey of EDAb was carried out in Sihui county of Gunagdong Province (the highest incidence area of NPC in China) and the city of Guangzhou using the methods previously established by our lab. In order to study the correlation between EDAb level and NPC, the titre of DEAb and their distribution in sera from 430 patients with NPC and 5030 normal persons were detected. It was found that the AER (level of EDAb was represented by the anti enzyme rate) of NPC patients gave a negative skew distribution and the Md=65.3% while the natural population (30 59 years old) gave a serious positive skew distribution and the Md is 7.9%. According to the pattern of EDAb distribution curve of 430 NPC patients and 2060 natural population. AER≥30% was defined as a cut off point between EDAb positive and negative. Using this value we got a rate of 90.7% (390/430) positive diagnosis in NPC patients, while in natural population the positive rate was 3.3% (68/2060), and in the IgA/VCA positive (1:5) normal person the positive rate was 6.0% (41/681). As to the other tumors including head and neck tumors the positive rate was 3.4% (7/204), similar to the natural population. After a period of 62 months of follow up surveillance, 15 of 224 EDAb positive normal persons found in the mass survey were diagnosed as NPC by histopathological examination. While in 4806 EDAb negative normal person only one case NPC patient was found in this period. 60% of these patients were diag nosed in their early stage of NPC. From these patients it was found that EDAb could appear in the sera of the patients as early as 62 months before NPC was definitely diagnosed. 2 of these patients were shown IgA/VCA negative and EDAb positive in mass survey. This suggested that in some of the precancerous patients EDAb could appear earlier than IgA/VCA. The signifi cance of the sera EDAb positivity of normal person was discussed.展开更多
Infectious mononucleosis is an acute illness due to Epstein Barr virus infection, which occurs commonly in young adults. Liver involvement in acute EBV infection occurs in up to 95% of patients between the 6th and 15t...Infectious mononucleosis is an acute illness due to Epstein Barr virus infection, which occurs commonly in young adults. Liver involvement in acute EBV infection occurs in up to 95% of patients between the 6th and 15th day of illness and is usually mild [1]. Here we report on a 7-year-old girl treated by Gastroenterology, Hepatology, and Nutrition Unit of Al-Adan Hospital pediatric Department, presented with prolonged fever, lymphadenopathy, generalized edema, hyperbilurubi- nemia and elevated liver enzymes secondary to EBV infection. This case represents a rare presentation of common viral infection in pediatric population.展开更多
Most adult humans have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the development of chronic fatigue syndrome. Stress is known to influence the immune system and can exacerbate the ...Most adult humans have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the development of chronic fatigue syndrome. Stress is known to influence the immune system and can exacerbate the sickness response. Although a role for psychological stress in the sickness response, particularly in combination with EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) has been established, and the role of physical stressors in these interactions remains unspecified. In this study, we seek to determine the interaction of chronic physical (swim) stress and EBV-encoded dUTPase injection. We hypothesize that a chronic physical stressor will exacerbate the sickness response following EBV-encoded dUTPase injection. To test this hypothesis mice receive daily injections of EBV-encoded dUTPase or vehicle and are subjected to 15 min of swim stress each day for 14 days or left unmanipulated. On the final evening of injections mice undergo behavioral testing. EBV-encoded dUTPase injection alone produces some sickness behaviors. The physical swimming stress does not alter the sickness response.展开更多
Most adult humans have been infected by Epstein-Barr virus (EBV), a putative cause of chronic fatigue syndrome, and carry latent EBV. The EBV-encoded dUTPase can induce sickness responses in mice and chronic stress ex...Most adult humans have been infected by Epstein-Barr virus (EBV), a putative cause of chronic fatigue syndrome, and carry latent EBV. The EBV-encoded dUTPase can induce sickness responses in mice and chronic stress exacerbates this response. Because individuals often adapt to chronic stress, we tested the hypothesis that acute restraint stress would potentiate these sickness responses elicited by EBV-encoded dUTPase. Male CD-1 mice were injected daily for one or three days with either saline or EBV-encoded dUTPase. Additionally, mice from each condition were either restrained for three hours daily or left undisturbed during the light phase when mice are inactive. Restraint decreased weight gain during the one- and three-day experiments. Restraint in saline injected mice increased anxiety-like behavior in the open field during the three-day experiment. There were no behavioral differences during the one-day experiment. Restraint stress had no effect when experienced acutely on one day, but did produce a sickness response after three days of exposure regardless of saline or dUTPase injection. In contrast to the effects of chronic stress and EBV-encoded dUTPase on the sickness response, acute stress did not affect sickness responses in association with EBV-encoded dUTPase. Thus, dUTPase does not appear to provoke the same sickness responses after acute stress as compared to chronic stress.展开更多
目的探讨传染性单核细胞增多症患儿调节性T细胞(regulatory T cell,Treg)/辅助性T细胞(helper T cell,Th)17免疫失衡与治疗后Epstein-Barr病毒(EBV)-DNA仍阳性的相关性,为传染性单核细胞增多症的治疗及预后评估提供重要标志物。方法以2...目的探讨传染性单核细胞增多症患儿调节性T细胞(regulatory T cell,Treg)/辅助性T细胞(helper T cell,Th)17免疫失衡与治疗后Epstein-Barr病毒(EBV)-DNA仍阳性的相关性,为传染性单核细胞增多症的治疗及预后评估提供重要标志物。方法以2021年1月至2023年6月就诊于秦皇岛市工人医院的88例传染性单核细胞增多症患儿作为研究对象。患儿接受基于阿昔洛韦或更昔洛韦的标准化治疗并持续随访,根据治疗14d时患儿EBV-DNA载量是否仍为阳性分为EBV-DNA阴性组(n=70)和EBV-DNA阳性组(n=18)。对比两组患儿一般临床资料、治疗相关特征、治疗前T细胞亚群、炎性细胞因子、免疫球蛋白等指标的差异。将单因素分析有意义的指标进行Spearman相关性分析及多因素Logistic回归分析,评价各差异性指标与传染性单核细胞增多症患儿治疗14d后EBV-DNA仍阳性的相关性和危险因素。结果EBV-DNA阳性组患儿平均住院时间、平均体温恢复时间、淋巴结肿大恢复时间均显著长于EBV-DNA阴性组患儿(P<0.05);EBV-DNA阳性组患儿平均CD4^(+)T淋巴细胞比例、CD4^(+)/CD8^(+)比值、Treg细胞比例、Treg/Th17比值、血清IL-4水平均显著低于EBV-DNA阴性组患儿,平均Th17细胞比例及血清IFN-γ水平均显著高于EBV-DNA阴性组患儿(P<0.05);多因素Logistic回归分析表明传染性单核细胞增多症患儿CD4^(+)T淋巴细胞比例及Treg细胞比例较低、Th17细胞比例较高及Treg/Th17比值较低均是规范治疗14d后EBV-DNA仍阳性的危险因素(P<0.05)。结论传染性单核细胞增多症患儿治疗前T细胞亚群比例特征、Treg/Th17免疫失衡严重程度、Th1/Th2细胞因子水平及免疫球蛋白水平与治疗14d后EBV-DNA仍阳性具有显著相关性,密切监测并促进患儿免疫-炎症水平恢复平衡对于提高传染性单核细胞增多症治疗预后具有重要临床意义。展开更多
Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear...Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.展开更多
Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients ...Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.展开更多
Nasopharyngeal carcinoma(NPC)is common in southern China and Southeast Asia.Epstein-Barr virus(EBV)infection is an important etiology for NPC,and EBV genome can be detected in almost all tumor tissues of NPC in this r...Nasopharyngeal carcinoma(NPC)is common in southern China and Southeast Asia.Epstein-Barr virus(EBV)infection is an important etiology for NPC,and EBV genome can be detected in almost all tumor tissues of NPC in this region.Plasma EBV DNA,when quantitatively analyzed using real-time polymerase chain reaction(PCR),has been developed as a biomarker for NPC.In this review,the different clinical applications of plasma EBV DNA in the management of NPC,including screening,monitoring,and prognostication,are discussed.In addition,the biological issues of circulating EBV DNA,including the molecular nature and clearance kinetics,are also explored.展开更多
Epstein Barr virus (EBV) positive mucocutaneous ulcers(EBVMCU) form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosu...Epstein Barr virus (EBV) positive mucocutaneous ulcers(EBVMCU) form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract (GIT). Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn's disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn's disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.展开更多
In 1964,a new herpesvirus,Epstein-Barr virus(EBV),was discovered in cultured tumor cells derived from a Burkitt lymphoma(BL)biopsy taken from an African patient.This was a momentous event that reinvigorated research i...In 1964,a new herpesvirus,Epstein-Barr virus(EBV),was discovered in cultured tumor cells derived from a Burkitt lymphoma(BL)biopsy taken from an African patient.This was a momentous event that reinvigorated research into viruses as a possible cause of human cancers.Subsequent studies demonstrated that EBV was a potent growth-transforming agent for primary B cells,and that all cases of BL carried characteristic chromosomal translocations resulting in constitutive activation of the c-MYC oncogene.These results hinted at simple oncogenic mechanisms that would make Burkitt lymphoma paradigmatic for cancers with viral etiology.In reality,the pathogenesis of this tumor is rather complicated with regard to both the contribution of the virus and the involvement of cellular oncogenes.Here,we review the current understanding of the roles of EBV and c-MYC in the pathogenesis of BL and the implications for new therapeutic strategies to treat this lymphoma.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
Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predomina...Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.展开更多
The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influen...The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen(HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.展开更多
Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although c...Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection (ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 μm in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD.展开更多
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.
文摘BACKGROUND Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression.The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas.We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU.Through this case,we aim to emphasize the importance of accurately distinguishing between the two conditions.CASE SUMMARY The patient presented with an incidental finding of a small bowel tumor during computed tomography(CT)examination performed for hematuria.The CT scan showed irregular thickening of the distal ileum,which was suggestive of a malignant small bowel tumor.An exploratory laparotomy revealed an 8-cm mass in the distal ileum;thus,a segment of the small intestine,including the mass,was resected.Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing,marked inflammatory cell infiltration,and large atypical lymphoid cells(positive for EBV-encoded small RNA).A final diagnosis of an EBV-MCU was established.The postoperative course was uneventful,and the patient was discharged on postoperative day 7.The patient remained recurrencefree until 12 mo after surgery.CONCLUSION This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.
文摘This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previously reported to be associated with EBV. These studies showed that J6-1 cells were also infected with HHV-6 as demonstrate at the DNA level by PCR and Southern blot hybridization and by expression of HHV-6 early membrane antigen on the J6-1 cell surface. Further characterization showed J6-1 was co-infected with EBV type 2. Generally, cells infected with EBV type 2 do not grow well in vitro. However, J6-1 , although difficult to maintain in vitro, has been grown for 15 years. Possibly, co-infection with HHV6 confers this property. In this regard, J6-1 cells exhibited density dependent growth which could be inhibited with an anti-HHV-6-MA monoclonal antibody(MAb). In contrast, anti-HHV-6-VCA MAb stimulated the J6-1 cell proliferation. Electron microscopic analysis showed that, morphologically, there were two types of J6-1 cell, one with lymphoblastoid features and one with a monocytoid appearance. Accordingly, the flow profile of the J6-1 cell line showed heterogeneity. with two populations comprised of CD15-, CD19+ cells with low light scatter(small cells) and a population with greater light scatter(larger cells) which was CD15+ , CD19+. The population was negative for progenitor cell markers(CD33, 34 ), and T cell markers. Southern analysis showed no T cell receptor rearrangement, however there was a clonal JH and kappa light chain expressing population. Glycocytochemical analysis showed several endogenous lectin receptors on the J6-1 cell surface: BSA-Xylose, BSA-Rhamnose, BSAGal. BSA-Lac. This cell line shares many characteristics with other monocytic/ lymphoblastoid cell lines isolated elsewhere and provides circumstantial evidence linking Herpes viruses, as least as co- factors,to leukemia cell growth.
文摘In order to explore the relationship between Epstein Barr virus (EBV) and pathogenesis of multiple myeloma (MM), the presence of EBV DNA in mononuclear cells of bone marrow (BMMC) and peripheral blood (PBMC) taken from 23 multiple myeloma patients who were neither posttransplanted nor HIV positive were examined by polymerase chain reaction (PCR). Meanwhile the presence of EBV EBERs in bioptic bone marrow's specimens of 4 MM patients were examined by in situ hybridization (ISH). Acute leukemia, aplastic anemia and malnourished anemia patients were taken as control. It showed EBV DNA detective rate in BMMC (69 6%) and in PBMC (39 1%) of MM patients were higher significantly than control groups (P<0 05). The positive signals of EBERs were located in BMMC and the EBV positive samples detected by ISH were consistent with those by PCR. The results indicate that EBV is closely correlated to pathogenesis of MM.
文摘In 1987, a mass survey of EDAb was carried out in Sihui county of Gunagdong Province (the highest incidence area of NPC in China) and the city of Guangzhou using the methods previously established by our lab. In order to study the correlation between EDAb level and NPC, the titre of DEAb and their distribution in sera from 430 patients with NPC and 5030 normal persons were detected. It was found that the AER (level of EDAb was represented by the anti enzyme rate) of NPC patients gave a negative skew distribution and the Md=65.3% while the natural population (30 59 years old) gave a serious positive skew distribution and the Md is 7.9%. According to the pattern of EDAb distribution curve of 430 NPC patients and 2060 natural population. AER≥30% was defined as a cut off point between EDAb positive and negative. Using this value we got a rate of 90.7% (390/430) positive diagnosis in NPC patients, while in natural population the positive rate was 3.3% (68/2060), and in the IgA/VCA positive (1:5) normal person the positive rate was 6.0% (41/681). As to the other tumors including head and neck tumors the positive rate was 3.4% (7/204), similar to the natural population. After a period of 62 months of follow up surveillance, 15 of 224 EDAb positive normal persons found in the mass survey were diagnosed as NPC by histopathological examination. While in 4806 EDAb negative normal person only one case NPC patient was found in this period. 60% of these patients were diag nosed in their early stage of NPC. From these patients it was found that EDAb could appear in the sera of the patients as early as 62 months before NPC was definitely diagnosed. 2 of these patients were shown IgA/VCA negative and EDAb positive in mass survey. This suggested that in some of the precancerous patients EDAb could appear earlier than IgA/VCA. The signifi cance of the sera EDAb positivity of normal person was discussed.
文摘Infectious mononucleosis is an acute illness due to Epstein Barr virus infection, which occurs commonly in young adults. Liver involvement in acute EBV infection occurs in up to 95% of patients between the 6th and 15th day of illness and is usually mild [1]. Here we report on a 7-year-old girl treated by Gastroenterology, Hepatology, and Nutrition Unit of Al-Adan Hospital pediatric Department, presented with prolonged fever, lymphadenopathy, generalized edema, hyperbilurubi- nemia and elevated liver enzymes secondary to EBV infection. This case represents a rare presentation of common viral infection in pediatric population.
文摘Most adult humans have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the development of chronic fatigue syndrome. Stress is known to influence the immune system and can exacerbate the sickness response. Although a role for psychological stress in the sickness response, particularly in combination with EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) has been established, and the role of physical stressors in these interactions remains unspecified. In this study, we seek to determine the interaction of chronic physical (swim) stress and EBV-encoded dUTPase injection. We hypothesize that a chronic physical stressor will exacerbate the sickness response following EBV-encoded dUTPase injection. To test this hypothesis mice receive daily injections of EBV-encoded dUTPase or vehicle and are subjected to 15 min of swim stress each day for 14 days or left unmanipulated. On the final evening of injections mice undergo behavioral testing. EBV-encoded dUTPase injection alone produces some sickness behaviors. The physical swimming stress does not alter the sickness response.
文摘Most adult humans have been infected by Epstein-Barr virus (EBV), a putative cause of chronic fatigue syndrome, and carry latent EBV. The EBV-encoded dUTPase can induce sickness responses in mice and chronic stress exacerbates this response. Because individuals often adapt to chronic stress, we tested the hypothesis that acute restraint stress would potentiate these sickness responses elicited by EBV-encoded dUTPase. Male CD-1 mice were injected daily for one or three days with either saline or EBV-encoded dUTPase. Additionally, mice from each condition were either restrained for three hours daily or left undisturbed during the light phase when mice are inactive. Restraint decreased weight gain during the one- and three-day experiments. Restraint in saline injected mice increased anxiety-like behavior in the open field during the three-day experiment. There were no behavioral differences during the one-day experiment. Restraint stress had no effect when experienced acutely on one day, but did produce a sickness response after three days of exposure regardless of saline or dUTPase injection. In contrast to the effects of chronic stress and EBV-encoded dUTPase on the sickness response, acute stress did not affect sickness responses in association with EBV-encoded dUTPase. Thus, dUTPase does not appear to provoke the same sickness responses after acute stress as compared to chronic stress.
文摘目的探讨传染性单核细胞增多症患儿调节性T细胞(regulatory T cell,Treg)/辅助性T细胞(helper T cell,Th)17免疫失衡与治疗后Epstein-Barr病毒(EBV)-DNA仍阳性的相关性,为传染性单核细胞增多症的治疗及预后评估提供重要标志物。方法以2021年1月至2023年6月就诊于秦皇岛市工人医院的88例传染性单核细胞增多症患儿作为研究对象。患儿接受基于阿昔洛韦或更昔洛韦的标准化治疗并持续随访,根据治疗14d时患儿EBV-DNA载量是否仍为阳性分为EBV-DNA阴性组(n=70)和EBV-DNA阳性组(n=18)。对比两组患儿一般临床资料、治疗相关特征、治疗前T细胞亚群、炎性细胞因子、免疫球蛋白等指标的差异。将单因素分析有意义的指标进行Spearman相关性分析及多因素Logistic回归分析,评价各差异性指标与传染性单核细胞增多症患儿治疗14d后EBV-DNA仍阳性的相关性和危险因素。结果EBV-DNA阳性组患儿平均住院时间、平均体温恢复时间、淋巴结肿大恢复时间均显著长于EBV-DNA阴性组患儿(P<0.05);EBV-DNA阳性组患儿平均CD4^(+)T淋巴细胞比例、CD4^(+)/CD8^(+)比值、Treg细胞比例、Treg/Th17比值、血清IL-4水平均显著低于EBV-DNA阴性组患儿,平均Th17细胞比例及血清IFN-γ水平均显著高于EBV-DNA阴性组患儿(P<0.05);多因素Logistic回归分析表明传染性单核细胞增多症患儿CD4^(+)T淋巴细胞比例及Treg细胞比例较低、Th17细胞比例较高及Treg/Th17比值较低均是规范治疗14d后EBV-DNA仍阳性的危险因素(P<0.05)。结论传染性单核细胞增多症患儿治疗前T细胞亚群比例特征、Treg/Th17免疫失衡严重程度、Th1/Th2细胞因子水平及免疫球蛋白水平与治疗14d后EBV-DNA仍阳性具有显著相关性,密切监测并促进患儿免疫-炎症水平恢复平衡对于提高传染性单核细胞增多症治疗预后具有重要临床意义。
基金supported by grants from the Natural Science Foundation of Guangdong Province,China(No.2015A030310033)the Health&Medical Collaborative Innovation Project of Guangzhou City,China(No.201400000001)the Key Laboratory Construction Project of Guangzhou City(No.121800085)
文摘Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.
基金supported by Grants from the National Natural Science Foundation of China(Nos.81372409,81402532)the Sun Yat-sen University Clinical Research 5010 Program(No.2012011)
文摘Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.
文摘Nasopharyngeal carcinoma(NPC)is common in southern China and Southeast Asia.Epstein-Barr virus(EBV)infection is an important etiology for NPC,and EBV genome can be detected in almost all tumor tissues of NPC in this region.Plasma EBV DNA,when quantitatively analyzed using real-time polymerase chain reaction(PCR),has been developed as a biomarker for NPC.In this review,the different clinical applications of plasma EBV DNA in the management of NPC,including screening,monitoring,and prognostication,are discussed.In addition,the biological issues of circulating EBV DNA,including the molecular nature and clearance kinetics,are also explored.
文摘Epstein Barr virus (EBV) positive mucocutaneous ulcers(EBVMCU) form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract (GIT). Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn's disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn's disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.
基金supported by a grant from the Cancer Research UK,London(Programme Award C5575/A15032)
文摘In 1964,a new herpesvirus,Epstein-Barr virus(EBV),was discovered in cultured tumor cells derived from a Burkitt lymphoma(BL)biopsy taken from an African patient.This was a momentous event that reinvigorated research into viruses as a possible cause of human cancers.Subsequent studies demonstrated that EBV was a potent growth-transforming agent for primary B cells,and that all cases of BL carried characteristic chromosomal translocations resulting in constitutive activation of the c-MYC oncogene.These results hinted at simple oncogenic mechanisms that would make Burkitt lymphoma paradigmatic for cancers with viral etiology.In reality,the pathogenesis of this tumor is rather complicated with regard to both the contribution of the virus and the involvement of cellular oncogenes.Here,we review the current understanding of the roles of EBV and c-MYC in the pathogenesis of BL and the implications for new therapeutic strategies to treat this lymphoma.
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 Research Grants of National Basic Research Program of China (973 Program, 2010CB529305)Innovation and Technology Support Programme, Hong Kong (ITS/214/12)
文摘Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.
基金supported by the Research Grants Council Area of Excellence grant (AoE/M-06/08)
文摘The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen(HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.
文摘Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection (ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 μm in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD.