Cytokine Gene Polymorphisms and Epstein-Barr Virus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3125-3125
Author(s):  
Ren Lin ◽  
Zhiping Fan ◽  
Ke Zhao ◽  
Qianli Jiang ◽  
Jing Sun ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Infection ◽  
Associated Diseases ◽  
Tnf Α ◽  
Cytokine Gene Polymorphisms ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Tgf Β1

Abstract Backgroud: Epstein-Barr virus (EBV) infection/reactivation and associated diseases remain common complications in recipients of HSCT, leading to severe end-organ diseases and malignance. Single nucleotide polymorphism (SNP) in cytokine genes is considered to be related with EBV-associated post-transplant lymphoproliferative disorders (PTLD) in solid-organ transplantation recipients. In this study, we analyzed the association between cytokine gene polymorphisms and EBV infection/reactivation or diseases in recipients undergoing allo-HSCT. Methods: A total of 233 patients who received allo-HSCT between March 2012 to December 2014 were enrolled in this study. Ten SNPs, including IL-1β -511 rs16944, IL-1RN +11100 rs315952, IL-2 -330 rs2069762, IL-4 -590 rs2243250, IL-10 -592 rs1800872, IL-12 +1188 rs3212227, TNF-α -308 rs1800629, TGF-β1-509 rs1800469, TGF-β1 +869 rs1800470, IFN-γ +874 rs2430561, were tested. The SNPs genotypes in patients with or without EBV infection/reactivation and associated diseases were compared. Besides, the risk factors for EBV infection/reactivation were studied. Results: Seventy-four patients developed EBV infection/reactivation. The patients with EBV infection/reactivation had higher frequencies of donor IL-1β -511 TT genotype, donor IL-4 -590 TT genotype and recipient TNF-α -308 GG genotype than those without (p=0.021, p=0.004, p=0.020, respectively) while the frequencies of donor IL-1β -511 CC genotype, donor IL-1RN +11100 TT genotype, donor IL-2 -330 TT genotype, donor IL-4 -590 CC genotype and recipient TNF-α-308 GA genotype in patients with EBV infection/reactivation were lower than those without (p=0.041, p=0.029, p=0.005, p=0.011, p=0.042, respectively). Multivariate analysis showed donor IL-4 -590TT genotype (p=0.016, HR=1.907, 95% CI =1.130-3.218) and recipient TNF-α -308GG genotype (p=0.002, HR=3.550, 95% CI=1.613-7.812) were risk factors for post-transplant EBV infection/reactivation while donor IL-1RN +11100TT genotype (p=0.001, HR=0.382, 95% CI=0.218-0.670) was protective factors for post-transplant EBV infection/reactivation. Twenty-one patients developed EBV-associated diseases. The patients who developed EBV-associated diseases had higher frequency of donor IFN-γ +874 AT genotype than those did not (p=0.027). On the contrary, the frequencies of donor IL-1β-511 CC genotype, donor IL-10 -592 AA genotype, donor IL-12 +1188 AA genotype and donor IFN-γ +874 AA genotype in patients with EBV-associated diseases were lower than those without (p=0.019, p=0.018, p=0.018, p=0.010, respectively). Conclusion: Several SNPs in cytokine genes might be associated with EBV infection/reactivation and the development of EBV-associated diseases in recipients of allo-HSCT. However, these association should be studied further. Disclosures No relevant conflicts of interest to declare.

scholarly journals Epstein-Barr Virus BZLF1-Mediated Downregulation of Proinflammatory Factors Is Essential for Optimal Lytic Viral Replication

2015 ◽  
Vol 90 (2) ◽  
pp. 887-903 ◽  
Author(s):  
Yuqing Li ◽  
Xubing Long ◽  
Lu Huang ◽  
Mengtian Yang ◽  
Yan Yuan ◽  
...  
Keyword(s):  
Viral Replication ◽  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Inflammatory Factors ◽  
Barr Virus ◽  
Ebv Infection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Proinflammatory Factors

ABSTRACTElevated secretion of inflammatory factors is associated with latent Epstein-Barr virus (EBV) infection and the pathology of EBV-associated diseases; however, knowledge of the inflammatory response and its biological significance during the lytic EBV cycle remains elusive. Here, we demonstrate that the immediate early transcriptional activator BZLF1 suppresses the proinflammatory factor tumor necrosis factor alpha (TNF-α) by binding to the promoter of TNF-α and preventing NF-κB activation. A BZLF1Δ207-210 mutant with a deletion of 4 amino acids (aa) in the protein-protein binding domain was not able to inhibit the proinflammatory factors TNF-α and gamma interferon (IFN-γ) and reduced viral DNA replication with complete transcriptional activity during EBV lytic gene expression. TNF-α depletion restored the viral replication mediated by BZLF1Δ207-210. Furthermore, a combination of TNF-α- and IFN-γ-neutralizing antibodies recovered BZLF1Δ207-210-mediated viral replication, indicating that BZLF1 attenuates the antiviral response to aid optimal lytic replication primarily through the inhibition of TNF-α and IFN-γ secretion during the lytic cycle. These results suggest that EBV BZLF1 attenuates the proinflammatory responses to facilitate viral replication.IMPORTANCEThe proinflammatory response is an antiviral and anticancer strategy following the complex inflammatory phenotype. Latent Epstein-Barr virus (EBV) infection strongly correlates with an elevated secretion of inflammatory factors in a variety of severe diseases, while the inflammatory responses during the lytic EBV cycle have not been established. Here, we demonstrate that BZLF1 acts as a transcriptional suppressor of the inflammatory factors TNF-α and IFN-γ and confirm that BZLF1-facilitated escape from the TNF-α and IFN-γ response during the EBV lytic life cycle is required for optimal viral replication. This finding implies that the EBV lytic cycle employs a distinct strategy to evade the antiviral inflammatory response.

scholarly journals Quantitative cytokine level of TNF-α, IFN-γ, IL-10, TGF-β and circulating Epstein-Barr virus DNA load in individuals with acute Malaria due to P. falciparum or P. vivax or double infection in a Malaria endemic region in Indonesia

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261923
Author(s):  
Insani Budiningsih ◽  
Yoes Prijatna Dachlan ◽  
Usman Hadi ◽  
Jaap Michiel Middeldorp
Keyword(s):  
Epstein Barr Virus ◽  
Rapid Test ◽  
Clear Correlation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Tnf Α ◽  
Ebv Dna ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Pcr Targeting

Plasmodium falciparum Malaria and Epstein-Barr Virus (EBV) infection are risk factors in the development of Burkitt’s lymphoma. In Indonesia, 100% of the population is persistently infected with EBV early in life and at risk of developing EBV-linked cancers. Currently, 10.7 million people in Indonesia are living in Malaria-endemic areas. This cross-sectional study was initiated to investigate how acute Malaria dysregulates immune control over latent EBV infection. Using blood and plasma samples of 68 patients with acute Malaria and 27 healthy controls, we measured the level of parasitemia for each plasmodium type (P. falciparum, P. vivax, and mixed) by microscopy and rapid test. The level of 4 regulatory cytokines was determined by quantitative ELISA and the level of circulating EBV genome by real-time PCR targeting the single copy EBNA-1 sequence. All Plasmodium-infected cases had high-level parasitemia (>1000 parasites/ul blood) except for one case. EBV-DNA levels were significantly more elevated in P. falciparum and P. vivax infections (P<0.05) compared to controls. EBV-DNA levels were not related to age, gender, Malaria symptoms, or plasmodium type. TNF-α and IL-10 levels were increased in Malaria cases versus controls, but IFN-γ and TGF- β levels were comparable between the groups. Only TNF-α levels in P. falciparum cases showed a clear correlation with elevated EBV DNA levels (R2 = 0.8915). This is the first study addressing the relation between EBV (re)activation and cytokine responses during acute Malaria, revealing a clear correlation between pro-inflammatory cytokine TNF-α and EBV-DNA levels, specifically in P. falciparum cases, suggesting this cytokine to be key in dysregulating EBV homeostasis during acute P. falciparum Malaria.

Epstein-Barr Virus Infection In Recipient Of Allogeneic Hematopoietic Stem Cell Transplantation: The Role Of Cytomegalovirus

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4555-4555
Author(s):  
Qifa Liu ◽  
Ren Lin ◽  
Can Liu ◽  
Meiqing Wu ◽  
Li Xuan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Research Funding ◽  
Epstein Barr Virus ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Ebv Infection ◽  
Associated Diseases ◽  
Ebv Dna ◽  
Epstein Barr

Background Epstein-Barr virus (EBV) infection is a common complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), leading to fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. A few studies suggested that cytomegalovirus (CMV) might play a role in PTLD. In this study, the effect of CMV on EBV DNA-emia and EBV-associated diseases was evaluated in the recipients of allo-HSCT. Methods Three hundred and fifty-two patients undergoing allo-HSCT were enrolled in this prospective study between July 2008 and June 2013. The EBV-DNA and CMV-DNA levels in blood and secretion were monitored by quantitative real-time polymerase chain reaction (RQ-PCR) before and in different time points after transplantation. EBV and CMV DNA-emia were diagnosed when EBV-DNA or CMV-DNA in the blood was positive twice consecutively. Results During the follow-up period, 99 patients (28.1%) developed EBV DNA-emia and 41 (11.6%) developed EBV-associated diseases including 27 EBV-associated PTLD and 14 other EBV-associated diseases. One hundred and fifty-nine patients (45.2%) developed CMV DNA-emia and 10 (2.8%) developed CMV-associated diseases. Of the 99 patients who developed EBV DNA-emia, 56 had CMV DNA-emia before EBV DNA-emia, and the median time from occurrence of CMV DNA-emia to EBV DNA-emia and EBV-associated diseases were 15 (range, 0-269) days and 26 (range, 0-255) days, respectively. Six patients developed co-existing CMV DNA-emia at the time of EBV-associated diseases diagnosed. DNA-emia before EBV infection had positive correlation with EBV DNA-emia (r=0.14, p=0.007) and EBV-associated diseases (r=0.15, p=0.005), but both correlation coefficients were weak. There was a strong positive correlation between EBV DNA-emia and EBV-associated diseases (r=0.56, p<0.001). The patients with CMV DNA-emia had a higher risk for developing EBV infection than those without (OR 2.279, 95% confidence interval [CI] 1.420-3.657, p=0.001). After EBV infection occurred, 15 patients developed CMV DNA-emia, including 4 developed CMV-associated diseases, at a median time of 33 days (range, 12-50 days). EBV infection was not related to CMV DNA-emia (p=0.87) or CMV associated diseases (p=0.27) occurring after EBV infection. Conclusion The results suggest that CMV may play a contributory role in the development of EBV DNA-emia and EBV-associated diseases. Disclosures: Liu: This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome

Blood ◽  
2005 ◽  
Vol 106 (9) ◽  
pp. 3090-3096 ◽  
Author(s):  
Huai-Chia Chuang ◽  
Jong-Ding Lay ◽  
Wen-Chuan Hsieh ◽  
Hui-Ching Wang ◽  
Yao Chang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Epstein Barr Virus ◽  
Cell Activation ◽  
Hemophagocytic Syndrome ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Th1 Cytokines

AbstractThe primary infection of Epstein-Barr virus (EBV) may result in fatal infectious mononucleosis or hemophagocytic syndrome (HPS) in 2 diseases; that is, X-linked lymphoproliferative disorder (XLP) and hemophagocytic lymphohistiocytosis (HLH). XLP is linked to mutations of the SAP/SH2D1A gene with dysregulated T-cell activation in response to EBV infection. Patients with sporadic HLH, however, usually have no mutation of the SAP/SH2D1A gene, and EBV latent membrane protein-1 (LMP1) can up-regulate Th1 cytokines in EBV-infected T cells. Since both diseases share common manifestations of HPS, it is important to clarify whether a cross-talk exists between signaling lymphocyte activation molecule (SLAM)–associated protein (SAP) and LMP1-mediated pathways to explain the common pathogenesis of HPS. In this study, no mutation of the SAP/SH2D1A gene at exon 2/3 was detected in 7 HLH cases. Interestingly, EBV LMP1 could transcriptionally inhibit the expression of SAP/SH2D1A and activate downstream molecules ERK and interferon-γ (IFN-γ). LMP1-mediated SAP/ERK/IFN-γ signals appear to act via the TNF receptor–associated factor (TRAF)2,5/nuclear factor κB (NF-κB) pathway, since dominantnegative TRAF2/5 and NF-κB inhibitor could rescue SAP expression and downregulate IFN-γ. Although HLH is genetically distinct from XLP, our data suggest that both diseases share a common signal pathway, through either the mutation or LMP1-mediated suppression of the SAP gene, leading to overt T-cell activation and enhanced Th1 cytokine secretion in response to EBV infection.

scholarly journals Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 288
Author(s):  
Pascal Roland Enok Bonong ◽  
Monica Zahreddine ◽  
Chantal Buteau ◽  
Michel Duval ◽  
Louise Laporte ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Infection ◽  
Relative Risks ◽  
Epstein Barr

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.

scholarly journals BZLF1 Attenuates Transmission of Inflammatory Paracrine Senescence in Epstein-Barr Virus-Infected Cells by Downregulating Tumor Necrosis Factor Alpha

2016 ◽  
Vol 90 (17) ◽  
pp. 7880-7893 ◽  
Author(s):  
Xubing Long ◽  
Yuqing Li ◽  
Mengtian Yang ◽  
Lu Huang ◽  
Weijie Gong ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Life Cycles ◽  
Inflammatory Factors ◽  
Necrosis Factor Alpha ◽  
Inflammatory Microenvironment ◽  
Barr Virus ◽  
Ebv Infection ◽  
Tnf Α ◽  
Factor Alpha ◽  
Epstein Barr

ABSTRACTRecent studies have shown that inflammatory responses trigger and transmit senescence to neighboring cells and activate the senescence-associated secretory phenotype (SASP). Latent Epstein-Barr virus (EBV) infection induces increased secretion of several inflammatory factors, whereas lytic infections evade the antiviral inflammatory response. However, the changes in and roles of the inflammatory microenvironment during the switch between EBV life cycles remain unknown. In the present study, we demonstrate that latent EBV infection in EBV-positive cells triggers the SASP in neighboring epithelial cells. In contrast, lytic EBV infection abolishes this phenotype. BZLF1 attenuates the transmission of paracrine senescence during lytic EBV infection by downregulating tumor necrosis factor alpha (TNF-α) secretion. A mutant BZLF1 protein, BZLF1Δ207-210, that cannot inhibit TNF-α secretion while maintaining viral transcription, fails to block paracrine senescence, whereas a neutralizing antibody against TNF-α is sufficient to restore its inhibition. Furthermore, latent EBV infection induces oxidative stress in neighboring cells, while BZLF1-mediated downregulation of TNF-α reduces reactive oxygen species (ROS) levels in neighboring cells, and ROS scavengers alleviate paracrine senescence. These results suggest that lytic EBV infection attenuates the transmission of inflammatory paracrine senescence through BZLF1 downregulation of TNF-α secretion and alters the inflammatory microenvironment to allow virus propagation and persistence.IMPORTANCEThe senescence-associated secretory phenotype (SASP), an important tumorigenic process, is triggered and transmitted by inflammatory factors. The different life cycles of Epstein-Barr virus (EBV) infection in EBV-positive cells employ distinct strategies to modulate the inflammatory response and senescence. The elevation of inflammatory factors during latent EBV infection promotes the SASP in uninfected cells. In contrast, during the viral lytic cycle, BZLF1 suppresses the production of TNF-α, resulting in the attenuation of paracrine inflammatory senescence. This finding indicates that EBV evades inflammatory senescence during lytic infection and switches from facilitating tumor-promoting SASP to generating a virus-propagating microenvironment, thereby facilitating viral spread in EBV-associated diseases.

HLA Polymorphisms and Epstein-Barr Virus Infection In The Recipient Of Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3291-3291
Author(s):  
Ren Lin ◽  
Qian Fan ◽  
Sijian Yu ◽  
Zhiping Fan ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Research Funding ◽  
Epstein Barr Virus ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Ebv Infection ◽  
Associated Diseases ◽  
Epstein Barr

Abstract Background Epstein-Barr virus (EBV) infection/reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cause fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. The development of EBV infection/reactivation and EBV-associated diseases are closely related to the immune function. Human leukocyte antigen (HLA) molecules are responsible for antigen processing and presentation to the immune system. Thus, it is supposed that HLA polymorphisms might be associated with EBV infection/reactivation and EBV-associated diseases. In this study, HLA polymorphisms and EBV infection/reactivation or EBV-associated diseases in the recipients of allo-HSCT were analyzed. Methods Three hundred and forty-nine recipients undergoing allo-HSCT were enrolled in this study between July 2008 to June 2013. For recipients and their donors, HLA-A, -B and HLA-DR were analyzed using PCR-sequence specific oligonueleotide probing (PCR-SSOP). The EBV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR). Results With a median follow-up of 389 days post-transplantation (range, 7 to 1828 days), 96 cases developed EBV infection/reactivation and 40 developed EBV-associated diseases including 27 EBV-PTLD and 13 other EBV-associated diseases (i.e. 7 fever, 1 pneumonia, 2 encephalitis, 1 hepatitis, 1 encephalitis accompanying pneumonia and 1 enteritis accompanying hepatitis). The 3-year cumulative incidence of EBV infection/reactivation and EBV-associated diseases were 29.1%±2.6% and 13.1%±2.0%, respectively. 43.8% of the recipients with HLA-A11 developed EBV infection/reactivation, compared with 56.5% of those without HLA-A11 (p=0.039). Multivariate analysis showed that HLA-A11 was a protective factor for EBV infection/reactivation (OR 0.497, 95% confidence interval [CI] 0.284-0.869, p=0.014). The recipients who had the donors with HLA-A31 had a higher incidence of EBV-associated diseases than those whose donors did not have HLA-A31 (10.3% vs. 2.9%, p=0.046); more patients carried HLA-B44 suffered EBV-associated diseases than those not carried HLA-B44 (7.7% vs. 1.3%, p=0.035). In multivariate analysis, recipient HLA-B44 were confirmed to be a risk factor for EBV-associated diseases (OR 17.749, 95% confidence interval [CI] 1.946-161.917, p=0.011). The incidence of PTLD in the recipients with HLA-A74 was 7.4%, compared with 0.6% in those without HLA-A74 (p=0.031); the incidences of PTLD in recipients whose donors had and did not have HLA-DR04 were 37.0% and 20.2%, respectively (p=0.042). Multivariate analysis showed that recipient HLA-A74 (OR 11.350, 95%CI: 1.119-115.178, p=0.040) and donor HLA-DR04 (OR 3.227, 95%CI: 1.323-7.873, p=0.010) were risk factors for development of PTLD. Conclusion Our data suggest that HLA polymorphisms might affect EBV infection/reactivation and EBV-associated diseases. Disclosures: Liu: This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Transfusion-Related Epstein-Barr Virus (EBV) Infection Among Stem Cell Transplant Recipients: a Retrospective Cohort Study In Children

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3340-3340 ◽  
Author(s):  
Helen Trottier ◽  
Carolina Alfieri ◽  
Nancy Robitaille ◽  
Michel Duval ◽  
Chantal Buteau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Blood Products ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Abstract Abstract 3340 Background: In many countries, numerous steps are taken to minimize the risk of infection from transfused blood or blood products. While the risk of transfusion-related infections such as HIV and HCV has become exceedingly rare, the risk of transfusion transmitted infectious diseases for which testing is not currently performed continues to be a major concern. Any infectious agent with a blood phase has the potential to be transmitted by transfusion. Among these untested microbial agents is Epstein-Barr virus (EBV/HHV-4), which, in the transplant setting, may cause lymphoproliferative disease, a potentially fatal cancer. Pediatric patients who are EBV-seronegative at the time of transplant are at high risk for developing this disease upon EBV infection during the early post-transplant period. Objective: Given that blood products are routinely administered to stem cell (includes bone marrow and cord-blood) transplant patients, this study was initiated to examine the incidence of transfusion-related post-transplant EBV infection in children receiving a stem cell graft. Methods: Patient charts were reviewed for: 1) the presence or absence of EBV antibodies (EBNA, VCA, EA) in pre-transplant sera from recipients and donors, 2) the incidence of post-transplant EBV infection (through PCR testing of recipients' blood), and 3) the characteristics of the children (age, sex, etc.) and their transfusion history. Results: Ste-Justine Hospital records revealed a total of 488 stem cell grafts performed on 429 patients between 1993 and 2009. Among these patients, 42% (179) were girls and 58% (250) were boys. The mean and median age at transplantation was 9.1 years (SD=6.1) and 8.8 years (IQR:3.6-14.5), respectively. Transplantations were subdivided into 3 categories: autologous (32%), allogeneic-cord blood (27%), allogeneic-other (41%). The seroprevalence of EBV was 80% and 66% in recipients and donors, respectively. Our data indicate that 25% of naïve recipients (no antibodies before transplantation) developed EBV viremia (positive PCR in blood) within a median time of 73 days following transplantation. Transmission of EBV may have occurred through virus contained either in the transplanted bone marrow or in the transfused blood products. Interestingly, EBV infection occurred in 16% of naïve recipients following cord-blood transplantation (known to be EBV negative). Barring natural infection, which is possible but unlikely, this strongly points to blood products as the vehicle for transmission. Conclusion: In view of the association between EBV and post-transplant lymphoproliferative disease, seen most often in patients who undergo primary EBV infection soon after transplant, the transmission of EBV via blood or blood products merits special consideration in further studies. Funding: FRSQ Grant #13904. Disclosures: No relevant conflicts of interest to declare.

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