The Impact of Epstein-Barr Virus Infection on Juvenile Idiopathic Arthritis Activity and Patient’s Response to Treatment

This study aimed to investigate the relationship between Epstein-Barr virus (EBV) infection and the onset of juvenile idiopathic arthritis (JIA), disease activity, and response to treatment. The study included 44 children with JIA, 23 children with different types of arthritis, and 44 controls. We measured EBV infection markers, including the EBV DNA load and the concentration of antibodies to viral antigens, at disease onset, before treatment. Six months after JIA diagnosis and the initiation of treatment patients with anti-viral capsid antigen IgG had a higher disease activity and worse response to treatment than patients without previous infection. After six months of treatment, the probability of disease inactivity in children without a history of EBV infection was almost 6.5 times greater than in a child with a history of infection. Furthermore, the probability of a better response after six months of treatment in a child with a history of EBV infection was more than five times smaller than in a child without infection. A past EBV infection can have a negative effect on achieving disease remission and may be associated with a worse response to treatment. Our results do not indicate the need for routine assessment of EBV infection markers in patients with JIA.

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An Absence of Epstein–Barr Virus Reactivation and Associations with Disease Activity in People with Multiple Sclerosis Undergoing Therapeutic Hookworm Vaccination

Vaccines ◽

10.3390/vaccines8030487 ◽

2020 ◽

Vol 8 (3) ◽

pp. 487

Author(s):

Peter A. C. Maple ◽

Bruno Gran ◽

Radu Tanasescu ◽

David I. Pritchard ◽

Cris S. Constantinescu

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Epstein Barr Virus ◽

Nuclear Antigen ◽

Virus Reactivation ◽

Serum Samples ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Reactivation ◽

Epstein Barr

Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship with disease activity in people with MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1) IgG, and EBV early antigen (EA) IgG. Disease activity was assessed by periodic MRI. Significance was set at p < 0.05. Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2% were EBV EA IgG positive. EBV antibody levels were generally stable, and EBV reactivation in PwMS was not demonstrated by significant increases in IgG titre over 12 months. Disease activity was most frequent in PwMS possessing high levels of EBV VCA IgG (>600 units/mL) or EBNA-1 IgG (>150 units/mL); however, there was no association with hookworm treatment. Interpretation: Therapeutic hookworm vaccination was not associated with EBV reactivation. Multiple sclerosis disease activity was associated with high levels of EBV VCA IgG or EBNA-1 IgG.

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The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.3121.3121 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3121-3121

Author(s):

Alexander Claviez ◽

Markus Tiemann ◽

Heike Lueders ◽

Reza Parwaresch ◽

Guenther Schellong ◽

...

Keyword(s):

Overall Survival ◽

Children And Adolescents ◽

Hodgkin’S Lymphoma ◽

Epstein Barr Virus ◽

Hodgkin's Lymphoma ◽

Barr Virus ◽

Ebv Infection ◽

Nodular Sclerosis ◽

Epstein Barr ◽

The Impact

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.

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Modulation of alternative splicing during early infection of human primary B lymphocytes with Epstein-Barr virus (EBV): a novel function for the viral EBNA-LP protein

Nucleic Acids Research ◽

10.1093/nar/gkab787 ◽

2021 ◽

Vol 49 (18) ◽

pp. 10657-10676

Author(s):

Evelyne Manet ◽

Hélène Polvèche ◽

Fabrice Mure ◽

Paulina Mrozek-Gorska ◽

Florian Roisné-Hamelin ◽

...

Keyword(s):

Alternative Splicing ◽

B Lymphocytes ◽

Splice Variant ◽

Epstein Barr Virus ◽

Human Herpesvirus ◽

Splicing Regulation ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

The Impact

Abstract Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers worldwide. Ex vivo, the virus efficiently infects resting human B lymphocytes and induces their continuous proliferation. This process is accompanied by a global reprogramming of cellular gene transcription. However, very little is known on the impact of EBV infection on the regulation of alternative splicing, a pivotal mechanism that plays an essential role in cell fate determination and is often deregulated in cancer. In this study, we have developed a systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes. Our results reveal that major modifications of alternative splice variant expression appear as early as day 1 post-infection and suggest that splicing regulation provides—besides transcription—an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. We also report a role for the viral proteins, EBNA2 and EBNA-LP, in the modulation of specific alternative splicing events and reveal a previously unknown function for EBNA-LP—together with the RBM4 splicing factor—in the alternative splicing regulation of two important modulators of cell proliferation and apoptosis respectively, NUMB and BCL-X.

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Acute renal failure secondary to EBV in a 21-year-old healthy male: a case report

KIDNEYS ◽

10.22141/2307-1257.10.3.2021.239599 ◽

2021 ◽

Vol 10 (3) ◽

pp. 181-183

Author(s):

Tom Saliba ◽

Albert Huard

Keyword(s):

Renal Failure ◽

Filtration Rate ◽

Epstein Barr Virus ◽

Spontaneous Recovery ◽

Healthy Male ◽

Clinical Exam ◽

Barr Virus ◽

Ebv Infection ◽

History Of ◽

Epstein Barr

Epstein-Barr virus (EBV) affects 9 out of 10 people at some point in their lives. Though generally a benign infection, it can present with a plethora of symptoms and complications. We present the case of a 21-year-old previously healthy male suffering from EBV who presented with an 8-day history of odynophagia, pharyngitis, cough, abdominal pain and fatigue, previously he also had a fever which reached a maximum of 38.5 °C. The patient’s clinical exam was positive only for abdominal tenderness. During his hospitalisation for EBV, our patient suffered sudden renal failure over the course of 4 days, with a glomerular filtration rate dropping to 33 mL/min/1.73 m2, before spontaneously recovering to normal levels. This occurred with supportive treatment only and without the use of corticosteroids. This case illustrates an atypical presentation of EBV infection and provides a further example of spontaneous recovery of renal function.

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The influence of human genetic variation on Epstein–Barr virus sequence diversity

Scientific Reports ◽

10.1038/s41598-021-84070-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sina Rüeger ◽

◽

Christian Hammer ◽

Alexis Loetscher ◽

Paul J. McLaren ◽

...

Keyword(s):

Genetic Variation ◽

Epstein Barr Virus ◽

Rare Variants ◽

Amino Acid Level ◽

Genomic Variation ◽

Human Genetic Variation ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

The Impact

AbstractEpstein–Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count < 200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.

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Reactivation of Epstein–Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4) infection during COVID-19: epidemiological features

Voprosy Virusologii ◽

10.36233/0507-4088-40 ◽

2021 ◽

Vol 66 (2) ◽

pp. 152-161

Author(s):

T. V. Solomay ◽

T. A. Semenenko ◽

N. N. Filatov ◽

S. L. Vedunova ◽

V. F. Lavrov ◽

...

Keyword(s):

Interstitial Pneumonia ◽

Reference Values ◽

Epstein Barr Virus ◽

Relative Number ◽

Barr Virus ◽

Ebv Infection ◽

Epidemiological Features ◽

Hospital Patients ◽

Epstein Barr ◽

Infection Markers

Introduction. Immunodeficiency underlying the development of severe forms of new coronavirus infection may be the result of mixed infection with SARS-CoV-2 and other pathogens, including Epstein–Barr virus (EBV).The aim is to study the prevalence and epidemiological features of co-infection with SARS-CoV-2 and EBV. Material and methods. A cross-sectional randomized study was conducted in Moscow region from March to May 2020. Two groups were examined for EBV-markers: hospital patients (n = 95) treated for SARS-CoV-2 infection and blood donors (n = 92).Results. With equal EBV prevalence the detection of active infection markers in donors (10.9%) was noticeably lower than in SARS-CoV-2 patients (80%). Significant differences in this indicator were also found when patients from subgroups with interstitial pneumonia with the presence (96.6%) and absence (97.2%) of SARS-CoV-2 in the nasopharyngeal smear were compared with the subgroup of patients with mild COVID-19 (43.3%). The average IgG VCA and IgG EBNA positivity coefficients in donor group were higher than in patient group (p < 0.05). Patients with active EBV infection markers were significantly more likely to have pneumonia, exceeding the reference values of ALT and the relative number of monocytes (odds ratio – 23.6; 3.5; 9.7, respectively).Discussion. The present study examined the incidence and analyzed epidemiological features of active EBV infection in patients with COVID-19.Conclusion. A significantly higher rate of detection of active EBV infection markers in hospital patients indicates a combined participation SARS-CoV-2 and EBV in the development of interstitial pneumonia. Low levels of specific IgG EBV serve as predictors of EBV reactivation. Exceeding the reference values of ALT and the relative number of monocytes in patients should serve as a reason for examination for active EBV infection markers.

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P-O12 Atraumatic Splenic Rupture Secondary to Concurrent Cytomegalovirus and Epstein Barr Virus Infection

British Journal of Surgery ◽

10.1093/bjs/znab430.122 ◽

2021 ◽

Vol 108 (Supplement_9) ◽

Author(s):

Catherine McCollum ◽

Khurram Khan ◽

Dhruv Sahni ◽

David Bell ◽

David Chong

Keyword(s):

Epstein Barr Virus ◽

Splenic Rupture ◽

Sudden Onset ◽

Cmv Infection ◽

Barr Virus ◽

Ebv Infection ◽

Life Threatening ◽

History Of ◽

Epstein Barr ◽

Atraumatic Splenic Rupture

Abstract Background Infectious Mononucleosis (IM) is a common viral illness among adolescents and young adults. While most cases are self-limiting, a small number of patient can develop life threatening complications, such as atraumatic splenic rupture (ASR). This is a rare but serious sequelae, and the commonest cause of associated mortality. While Epstein Barr Virus is commonly associated with IM, concurrent infection of cytomegalovirus (CMV) and EBV is rarely reported. Both infections are associated with splenomegaly, however this is usually mild and very rarely results in ASR. Methods We present the case of an immunocompetent nineteen year old male who underwent emergency splenectomy for ASR secondary to concurrent EBV and CMV infection. He presented to the Emergency Department with a five hour history of severe, sudden onset left upper quadrant pain preceded by coughing fit. He reported a one year history of incidental splenomegaly and recent positive monospot test in community. Computerised tomography (CT) of abdomen and pelvis confirmed splenic rupture with large haemo-peritoneum and large sub-capsular haematoma. He was haemodynamically unstable and underwent laparotomy and splenectomy. Results Intraoperative findings included two litres of intraperitoneal blood and large spleen with sub-capsular haematoma; approximately seventeen centimetre diameter and weighed nine hundred and seventy grams. Pathology showed features of non-specific lymphoid hyperplasia. Serum virology confirmed high levels of CMV on polymerase chain reaction with low levels of EBV detected. Virology screening was incidentally repeated post discharge and at this time was consistent acute EBV infection. No alternative cause for splenic rupture or pre-existing splenomegaly has been identified. Conclusions The serology results in this case confirm acute CMV infection with most likely concurrent EBV infection. While we cannot confidently identify which virus caused splenic rupture in this case, ASR is a life threatening condition and an important differential in patients presenting with sudden onset LUQ pain and shock. Splenectomy remains the treatment of choice in haemodynamically unstable patients.

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The influence of human genetic variation on Epstein-Barr virus sequence diversity

10.1101/2020.12.02.20242370 ◽

2020 ◽

Author(s):

Sina Rüeger ◽

Christian Hammer ◽

Alexis Loetscher ◽

Paul J McLaren ◽

Dylan Lawless ◽

...

Keyword(s):

Genetic Variation ◽

Epstein Barr Virus ◽

Rare Variants ◽

Amino Acid Level ◽

Genomic Variation ◽

Human Genetic Variation ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

The Impact

AbstractEpstein-Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4+ T cell count <200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.

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Epstein-Barr virus infection in ulcerative colitis: a clinicopathologic study from a Chinese area

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820930124 ◽

2020 ◽

Vol 13 ◽

pp. 175628482093012

Author(s):

Shu Xu ◽

Haiyang Chen ◽

Xiaoman Zu ◽

Xiuxue Hao ◽

Rui Feng ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Epstein Barr Virus ◽

Outcome Prediction ◽

Pcr Analysis ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr

Background: Opportunistic Epstein–Barr virus (EBV) infection in patients with ulcerative colitis (UC) has attracted increasing attention. This study aimed to evaluate the clinicopathological characteristics and clinical outcomes of UC with intestinal EBV infection and to explore the predictive value of blood EBV DNA for the presence of EBV in the intestine. Methods: Both peripheral blood and intestinal biopsies from 92 consecutive UC inpatients were included in this study. Normal colonic mucosal tissues from 20 colon cancer patients were used as controls. EBV testing and assessment were performed by EBV-DNA polymerase chain reaction (PCR), EBV-encoded small RNA in situ hybridization (EBER-ISH) and immunohistochemistry. Results: A total of 36 patients (39.1%) had UC with superimposed EBV colitis [EBER greater than 2/high-power field (HPF)]. EBER counts and disease activity were significantly correlated ( p < 0.05). The major endoscopic findings revealed more irregular and longitudinal ulcers in patients with superimposed EBV colitis ( p = 0.016, p = 0.021, respectively). Age, steroid dependence, and irregular ulcerations were identified as possible risk factors. The best EBER cut-off point for outcome prediction was 2.5/HPF. At a cut-off value of 2035 copies/ml, the sensitivity and specificity of the blood EBV-DNA PCR analysis for predicting EBV presence in the intestine were 76.5% and 68.5%, respectively. EBV-infected cells in UC with high EBV concentrations mainly included B lymphocytes by clinicopathology, and the infection might have progressed from the latent to the lytic phase of the EBV life cycle. Conclusion: The EBER count is positively correlated with disease activity. The best cut-off point for outcome prediction is 2.5/HPF. A high EBV viremia load may effectively predict EBV presence in the colonic mucosa.

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