Antibody against Epstein-Barr virus DNA polymerase activity in sera of patients with nasopharyngeal carcinoma

A salt-dependent DNA polymerase activity was demonstrated in the culture of an EBV-producing, lymphoblastoid cell line (NPC-204 cells) treated with 5-iodo-2'-deoxyuridine (IUdR). There was a high frequency of levels of antibody to this enzyme in sera of patients with nasopharyngeal carcinoma (NPC). In contrast, sera from healthy subjects had little or no neutralizing activity. The high antibody level appeared as early as stage 1 of the disease in many NPC patients. The levels of the antibody increased with the progression of the disease and declined in treated patients. The results strongly suggest that tests measuring serum antibody against EBV DNA polymerase activity can be used for early diagnosis and prognosis of NPC.     

Impaired late suppression of Epstein-Barr virus (EBV)-induced immunoglobulin synthesis: A common feature of autoimmune disease

We examined regulation of Epstein-Barr virus-induced plaque-forming cell generation in peripheral blood mononuclear cells from several autoimmune and seronegative diseases and correlated these results with Epstein-Barr virus-induced proliferation. We confirmed the defective regulation of Epstein-Barr virus-induced plaque-forming cells in peripheral blood mononuclear cells of patients with rheumatoid arthritis and scleroderma. Peripheral blood mononuclear cells from patients with seronegative arthropathies and chronic infective inflammation (cystic fibrosis) had normal regulation of Epstein-Barr virus-induced plaque-forming cells. Peripheral blood mononuclear cells from rheumatoid arthritis had excessive plaque-forming cell generation in the face of a normally regulated decrease in Epstein-Barr virus-induced proliferation. In contrast, peripheral blood mononuclear cells from scleroderma had defective suppression of both Epstein-Barr virus-induced proliferation and plaque-forming cell generation. Thus, impaired regulation of Epstein-Barr virus-induced plaque-forming cell generation is a common feature of autoimmune disease and demonstrates some specificity for these disorders.     

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large,multi-centre study

Epstein–Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.     

Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

茶多酚与亚硒酸钠联合对EBV抗原表达的抑制作用

用间接免疫荧光法测定Ｒａｊｉ细胞和Ｂ９５－８细胞ＥＢ病毒抗原的表达。结果显示无细胞毒浓度的茶多酚与亚硒酸钠联合对Ｒａｊｉ细胞ＥＢＶ－ＥＡ表达有显著的抑制作用,优于单纯茶多酚或亚硒酸钠的抑制作用。两药显示相互协同增效的作用 。抑制率与药物浓度相关;单纯茶多酚对Ｂ９５－８细胞ＥＢＶ－ＶＣＡ表达无抵制作用,但茶多酚能增强亚硒酸钠对Ｂ９５－８细胞ＥＢＶ－ＶＣＡ表达的抵制作用,抑制率随药物浓度的升高而升高。     

EBV-DNA检测在血液肿瘤性疾病中的应用价值

EB病毒 (EBV)属人类疱疹病毒 ,与人类多种疾病相关联。目的 　本研究探讨EB病毒感染与恶性血液病的关系。方法 　应用PCR法检测 38例血液肿瘤性疾病患儿骨髓细胞EBV -DNA。结果38例患儿骨髓EBV -DNA阳性检出率 6 1 % ( 2 3/38)。5例恶性淋巴瘤患儿均为阳性 ,急性白血病 (AL)、骨髓增生异常综合征 (MDS)、再生障碍性贫血 (AA)、特发性血小板减少性紫癜 (ITP)患儿阳性率较高 ,其余病例均为阴性。对照组 1 0例非血液病发热患儿仅 1例阳性。结论 　EBV感染与血液肿瘤性疾病的发生、发展及愈后关系密切。EBV感染可促使病情恶化或难治。同时对伴有不明原因发热的患儿除考虑肿瘤性发热外 ,应警惕因免疫功能异常导致的EBV易感因素 ,尽早动态检测EBV -DNA ,及时合理治疗。由于病人免疫力低下 ,对EBV病毒的免疫应答功能降低 ,抗体反应法作EBV常造成假阳性结果。本方法简便、快速、特异、敏感 ,具有重要的临床应用价值。     

Treatment response with sirolimus for a pediatric patient with an EBV‐associated smooth‐muscle tumor after bone marrow transplantation

Epstein–Barr virus–associated smooth‐muscle tumors (EBV‐SMTs) are unique and rare neoplasms described in immunocompromised patients. The case describes a nine‐year‐old female with a history of acute lymphoblastic leukemia with relapse and subsequent allogeneic bone marrow transplantation who presented with multiple EBV‐SMTs of the liver. EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short‐term response. We now report an extended treatment response with sirolimus in a pediatric patient with an EBV‐SMT.     

High mobility group box 1 (HMGB1) is upregulated by the Epstein-Barr virus infection and promotes the proliferation of human nasopharyngeal carcinoma cells

Conclusion: The current study confirmed the significant high mobility group box 1 (HMGB1) was promoted in human nasopharyngeal carcinoma (NPC) tissues by Epstein-Barr virus (EBV) infection, in association with the malignant status of NPC, and promoted the proliferation NPC cells RAGE-dependently. Objectives: The present study was to examine the association of HMGB1 over-expression in human NPC with the EBV-positivity and to determine the regulatory role of HMGB1 on the proliferation of NPC cells in vitro. Methods: Real-time PCR and Western blotting were utilized to examine the HMGB1 expression. EBV infection in CNE-2 cells was performed to investigate the HMGB1 promotion by EBV infection. RNA interference technology was utilized for the RAGE knockout. Results: It was demonstrated that HMGB1 was significantly higher in both mRNA and protein levels in the EBV-positive NPC tissues, in marked association with the malignant status of NPC, and with the LMP1 DNA level in EBV-positive NPC samples. In addition, the MTT assay, growth curve, and the colony forming assay confirmed the promotion by HMGB1 to the proliferation of CNE-2 cells, depending on RAGE.