scholarly journals Frequent co-reactivation of Epstein–Barr virus in patients with cytomegalovirus viremia under immunosuppressive therapy and/or chemotherapy

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052097288
Author(s):  
Yuki Hatayama ◽  
Yuki Hashimoto ◽  
Toru Motokura
Keyword(s):  
Immunosuppressive Therapy ◽  
Epstein Barr Virus ◽  
Quantitative Real Time Pcr ◽  
Old Patients ◽  
Steroid Pulse ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Immunosuppressed Patients ◽  
Ebv Dna ◽  
Epstein Barr

Objective Co-reactivation of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) occurs in iatrogenically immunosuppressed patients, but the clinical relevance of this is unknown. We aimed to determine the frequency of EBV reactivation in patients with CMV viremia and to explore its clinical significance. Methods Serum or plasma CMV and EBV DNA was detected by quantitative real-time PCR in 82 patients who received immunosuppressive therapy and/or chemotherapy and underwent CMV antigenemia tests. Results CMV DNA was positive in 55 patients, with EBV reactivation being found in 29 of these (52.7%). EBV co-reactivation was significantly associated with aging (>64 years vs. ≤64 years, odds ratio 4.07, 95% confidence interval 1.06–15.6). When older patients were divided into two groups according to age, EBV co-reactivation occurred more frequently in early-old patients (aged 65–74 years) than in late-old patients (aged ≥75 years) (100.0% vs. 53.3%, respectively). Steroid pulse treatment was administered significantly more often in the early-old group than in those aged ≤64 years and ≥75 years (72.7% vs 27.6% vs 14.3%, respectively). Conclusions Co-reactivation of EBV in patients with CMV viremia highlighted early-old patients and may reflect treatment intensity as well as immunosenescence.

scholarly journals Points of Recombination in Epstein-Barr Virus (EBV) Strain P3HR-1-Derived Heterogeneous DNA as Indexes to EBV DNA Recombinogenic Events In Vivo

2008 ◽  
Vol 82 (23) ◽  
pp. 11516-11525 ◽  
Author(s):  
Kazufumi Ikuta ◽  
Shamala K. Srinivas ◽  
Tim Schacker ◽  
Jun-ichi Miyagi ◽  
Rona S. Scott ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Lymphoid Cells ◽  
Defective Interfering Particles ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Pcr Products ◽  
Ebv Dna ◽  
Epstein Barr

ABSTRACT Deletions and rearrangements in the genome of Epstein-Barr virus (EBV) strain P3HR-1 generate subgenomic infectious particles that, unlike defective interfering particles in other viral systems, enhance rather than restrict EBV replication in vitro. Reports of comparable heterogeneous (het) DNA in EBV-linked human diseases, based on detection of an abnormal juxtaposition of EBV DNA fragments BamHI W and BamHI Z that disrupts viral latency, prompted us to determine at the nucleotide level all remaining recombination joints formed by the four constituent segments of P3HR-1-derived het DNA. Guided by endonuclease restriction maps, we chose PCR primer pairs that approximated and framed junctions creating the unique BamHI M/B1 and E/S fusion fragments. Sequencing of PCR products revealed points of recombination that lacked regions of extensive homology between constituent fragments. Identical recombination junctions were detected by PCR in EBV-positive salivary samples from human immunodeficiency virus-infected donors, although the W/Z rearrangement that induces EBV reactivation was frequently found in the absence of the other two. In vitro infection of lymphoid cells similarly indicated that not all three het DNA rearrangements need to reside on a composite molecule. These results connote a precision in the recombination process that dictates both composition and regulation of gene segments altered by genomic rearrangement. Moreover, the apparent frequency of het DNA at sites of EBV replication in vivo is consistent with a likely contribution to the pathogenesis of EBV reactivation.

scholarly journals Prevention of Epstein-Barr virus–lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4364-4369 ◽  
Author(s):  
Joost W. J. van Esser ◽  
Hubert G. M. Niesters ◽  
Bronno van der Holt ◽  
Ellen Meijer ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
High Risk ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Viral Reactivation ◽  
Preemptive Therapy ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Risk Patients ◽  
Ebv Dna ◽  
Epstein Barr

Recipients of a partially T-cell–depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV–lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite pre-emptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% ± 9% versus 49% ± 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% ± 10%, respectively) (P = .04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD.

scholarly journals The frequency of Epstein-Barr virus among hemodialysis patients, Ahvaz, Iran

2019 ◽  
Author(s):  
Rahil Nahid Nahid Samiei ◽  
Shahab Mahmoudvand ◽  
Somayeh Shokri ◽  
Manoochehr Makvandi ◽  
Heshmatol- lah Shahbazian ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Epstein Barr Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibody ◽  
Cross Sectional ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Study Results ◽  
Ebv Dna ◽  
Epstein Barr

Background and Objectives: Epstein-Barr virus (EBV) has infected more than 90% of adults worldwide. EBV infection is asymptomatic in healthy individuals and is controlled by a robust immune response while in individuals with weakened immunesystems including Hemodialysis (HD) patients and transplant recipients leads to serious illnesses. This study was aimed to investigate the frequency of EBV among the HD patients. Materials and Methods: The cross-sectional study was carried out on 84 HD patients. These sera were checked for an- ti-EBV (VCA) IgG Ab assessment using enzyme-linked immunosorbent assay (ELISA). The DNA was extracted from the sera samples and tested for EBV DNA using nested PCR. Results: 52/84 (61.9%) of HD were males and 32/84 (38.1%) were females. The average age of participants was varying from 18 to 85 years while the mean age was 52 ± 1.57 SD years. 81 of 84 (96.42%); including 49/52 (94.23%) male and 32/32 (100%) female, were positive for anti-EBV (VCA) IgG antibody while 3 (3.58%) were negative. No significant dif- ferences were observed between the subjects regarding gender (P=0.28). EBV DNA was detected in 7 (8.33%) individuals, including 6 (11.53%) and 1 (3.12%) in male and female, respectively (P=0.24). Conclusion: Our study results showed that high prevalence of anti-EBV (VCA) IgG antibody (96.42%) were observed among the HD patients. Although the status of EBV latency was not performed, but it seems many of these patients are at risk of EBV-reactivation during the organ transplantation. As a result, it is recommended that the detection of EBNA-1 gene as a marker of EBV latency should be implemented for all HD patients to prevent EBV reactivation during organ transplantation.

scholarly journals Interferon-alpha-2a as a salvage treatment for hemorrhagic enteritis associated with Epstein-Barr Virus reactivation : a case report

2021 ◽  
Vol 84 (1) ◽  
pp. 129-130
Author(s):  
D Lankenau-Vela ◽  
F De la Garza-Salazar ◽  
P Colunga-Pedraza ◽  
D Jaime-Villalón
Keyword(s):  
Interferon Alpha ◽  
Epstein Barr Virus ◽  
Salvage Treatment ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Immunosuppressed Patients ◽  
Hemorrhagic Enteritis ◽  
Epstein Barr ◽  
Almost All

Epstein-Barr virus [EBV] is a virus that infects almost all humans worldwide. After the acute phase of the infection, it stays in a latent form in B lymphocytes. EBV reactivation tends to occur in immunosuppressed patients. EBV reactivation may involve the gastrointestinal tract ; it has been associated mainly with colitis, but hemorrhagic enteritis has been poorly reported. Treatment usually includes antivirals. However, our patient did not respond to conventional treatment, so interferon alpha-2a was given as a salvage treatment. To our knowledge, this is the first reported case of hemorrhagic enteritis associated to EBV reactivation treated successfully with interferon alpha-2a.

Successful Treatment of Epstein-Barr Virus-Associated Lymphoproliferative Disorder with Rituximab in a Patient Undergoing Immunosuppressive Therapy for Aplastic Anemia

2016 ◽  
Vol 136 (3) ◽  
pp. 174-177
Author(s):  
Hiroaki Shimizu ◽  
Nobuhiko Kobayashi ◽  
Masahiro Mihara ◽  
Hirono Iriuchishima ◽  
Takuma Ishizaki ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Lymphoproliferative Disorder ◽  
Epstein Barr Virus ◽  
Transplant Recipients ◽  
Allogeneic Transplant ◽  
Barr Virus ◽  
Systemic Lymphadenopathy ◽  
Ebv Dna ◽  
Epstein Barr

Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is a currently emerging serious complication in immunosuppressed patients, especially in allogeneic transplant recipients. Several fatal cases of EBV-LPD have been reported in aplastic anemia (AA) patients receiving immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine A (CsA), but no appropriate prophylactic or therapeutic strategy has been established. Herein, we describe a 29-year-old man whose EBV-LPD was successfully treated with rituximab. He received IST with ATG plus CsA for hepatitis-associated AA. EBV-DNA in plasma, which was not detectable before IST, gradually increased after IST initiation. A high fever and systemic lymphadenopathy developed 31 days after IST initiation. An EBV-DNA titer of 5.7 × 105 copies/μl was detected, and a diagnosis of EBV-LPD was made. Although discontinuation of IST was not effective, a single dose of rituximab on day 33 resolved the clinical symptoms and completely eliminated EBV-DNA. Even after restarting CsA administration, no elevation of EBV-DNA was observed, and his complete blood cell count had fully recovered 1 year after IST. This case suggests that this treatment strategy for EBV-LPD with EBV-DNA monitoring and rituximab administration, which has been recommended in allogeneic transplant recipients, may also be useful in the context of AA patients receiving IST.

Quantitative analysis of circulating cell-free Epstein-Barr virus (EBV) DNA levels in patients with EBV-associated lymphoid malignancies

2000 ◽  
Vol 111 (1) ◽  
pp. 239-246 ◽  
Author(s):  
Kenny I. K. Lei ◽  
Lisa Y.S. Chan ◽  
Wing Y. Chan ◽  
Philip J. Johnson ◽  
Y. M. Dennis Lo
Keyword(s):  
Quantitative Analysis ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Lymphoid Malignancies ◽  
Ebv Dna ◽  
Epstein Barr

Association of normal oral mucosa with DNA of the main types of oncogenic viruses

2020 ◽  
pp. 60-63
Author(s):  
S.I. Kutukova ◽  
A.B. Chukhlovin ◽  
A.I. Yaremenko ◽  
Yu.V. Ivaskova ◽  
A.Ya. Razumova ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Epstein Barr Virus ◽  
Oncogenic Viruses ◽  
Viral Dna ◽  
Dna Viruses ◽  
Normal Oral Mucosa ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Hpv 18

The aim of the study was to assess the prevalence of DNA viruses (HSV I and II, CMV, EBV, HPV6.11, HPV16 and HPV18) in the native oral mucosa of healthy volunteers (n=50; 30 men (60.0%), 20 women (40.0%); 25—74 years, median age — 55.0 years (95% CI 47.60-56.76)). All samples of the normal oral mucosa were detected by real-time PCR to detect viral DNA. The majority of the examined — 76% (33/50) — revealed the DNA: one type of viral DNA in 17 (38.00%) of the examined, a combination of the two types in 14 (28.00%). In the normal oral mucosa, DNA of Epstein-Barr virus was significantly more often detected: 15 (30.00%) (p = 0.0276) and human papilloma viruses 27 (54.00%) (p <0.0001), especially HPV-18 (24 (48.00%)): mono-association in 9 (18.00%) examined and in 7 (14.00%) in combination with EBV DNA (p = 0.0253).

scholarly journals Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Disease Stage ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment ◽  
Moroccan Patients

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

scholarly journals Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer

2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Viral Load ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Tumor Volume ◽  
Nasopharyngeal Cancer ◽  
Dna Quantification ◽  
Barr Virus ◽  
Nasopharyngeal Biopsy ◽  
Ebv Dna ◽  
Epstein Barr

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

scholarly journals Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-Jie Chen ◽  
Wen-Na Xu ◽  
Hai-Yun Wang ◽  
Xiao-Xia Chen ◽  
Xue-Qi Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Screening Program ◽  
Southern China ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

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