scholarly journals Importance of Epstein–Barr virus infection in pathogenesis of proliferative complications in children with endogenous uveitis

2020 ◽  
Vol 9 (5-6) ◽  
pp. 800-804
Author(s):  
M. S. Petrovskaya ◽  
G. I. Krichevskaya ◽  
E. V. Denisova ◽  
L. A. Katargina ◽  
I. G. Kulikova

Endogenous uveitis (EU) in children is a multifactorial sight-threatening disease that reduces patient’s quality of life. Proliferative syndrome (PS) coupled to developing adhesions, opacity of vitreous body, epiretinal and preretinal membranes is one of the most serious EU complications, with yet-unknown pathogenesis. Among the numerous trigger factors, a role for infections, particularly human herpes group-driven, is proposed. The goal of the study was to assess a potential role of Herpes simplex viruses type 1 (HSV-1), Herpes simplex viruses type 2 (HSV-2), Epstein–Barr virus (EBV) and Cytomegalovirus (CMV) played in the PS pathogenesis in children with endogenous uveitis. 112 patients aged 3–17 years (mean age 10 years) with (93 patients)/without PS (19 children) were examined. IgM and IgG antibodies (markers of chronic and active infection) against HSV-1/2, EBV and CMV were detected by ELISA. A significantly increased PS rate in infected vs. uninfected children was revealed solely for EBV infection (p = 0.03), but not for HSV-1/2 (p > 0.05) or CMV-positive patients (p > 0.05). However, PS emergence in EBV-negative patients also suggests that some factors might contribute to proliferation in intraocular inflammation. In addition, level of serum IL-8 and IL-6 were assessed by multiplex analysis in 28 children. It was found that IL-8 was detected in all patients, with great individual fluctuations (5.6–2743 pg/ml). Enhanced systemic IL-8 level tended to rise in patients with more prominent proliferation and serological markers of EBV reactivation. However, serum IL-6 was detected by about 2-fold less often reaching up to 55% cases (variation of individual indices 1.3–35.5 pg/ml). A correlation between PS severity, EBV infection activity and systemic IL-6 level was not observed. Further studies evaluating a role of EBV infection in PS pathogenesis pediatric endogenous uveitis are necessary, as it may underlie a rationale for including antiherpetic drugs into a combination therapy.

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Zuhal Yesilbag ◽  
Asli Karadeniz ◽  
Fatih Oner Kaya

Primary Epstein-Barr virus (EBV) infection is almost always a self-limited disease characterized by sore throat, fever, and lymphadenopathy. Hepatic involvement is usually characterized by mild elevations of aminotransferases and resolves spontaneously. Although isolated gallbladder wall thickness has been reported in these patients, acute acalculous cholecystitis is an atypical presentation of primary EBV infection. We presented a young women admitted with a 10-day history of fever, nausea, malaise who had jaundice and right upper quadrant tenderness on the physical examination. Based on diagnostic laboratory tests and abdominal ultrasonographic findings, cholestasis and acute acalculous cholecystitis were diagnosed. Serology performed for EBV revealed the acute EBV infection. Symptoms and clinical course gradually improved with the conservative therapy, and at the 1-month follow-up laboratory findings were normal. We reviewed 16 adult cases with EBV-associated AAC in the literature. Classic symptoms of EBV infection were not predominant and all cases experienced gastrointestinal symptoms. Only one patient underwent surgery and all other patients recovered with conservative therapy. The development of AAC should be kept in mind in patients with cholestatic hepatitis due to EBV infection to avoid unnecessary surgical therapy and overuse of antibiotics.


Author(s):  
O. Abrahamovych ◽  
U. Abrahamovych ◽  
S. Guta ◽  
M. Farmaha ◽  
L. Kobak

Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by various manifestations and clinical course, many aspects of the etiology and pathogenesis of which remain unclear. Recently, the interest of researchers in studying the role of cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been growing in the occurrence and course of a number of human diseases due to their ability to affect almost all organs and systems of the body, causing the formation of latent, active or chronic infection, which can often cause temporary disability, disability or even death, however, for the patients with SLE, despite the possibility of approaching the difficult problem of diagnosis and treatment of this disease, this issue is given insufficient attention, as evidenced by isolated studies.The aim of the study. Detect cytomegalovirus and Epstein - Barr infection in patients with systemic lupus erythematosus and its dependence on gender and age of patients. Materials and methods of research. The study involved 120 patients (15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years with SLE, who were in the rheumatology department of the Communal Non-Commercial Enterprise of the Lviv Regional Council "Lviv Regional Clinical Hospital" in 2014-2019. To diagnose CMV and EBV infection by enzyme-linked immunosorbent assay, antibodies of IgM and IgG to viruses were detected in blood serum, and viruses were detected by polymerase chain reaction. According to the results of virus detection, formed groups of the patients, namely: patients with active CMV infection, active EBV, active CMV and EBV, without active CMV and EBV. All patients with SLE included in the study were subsequently stratified by age according to the classification of the World Health Organization (2015), according to which the following age limits were determined: young age, middle-aged, elderly, senile. Statistical analysis was performed on a personal computer in MS Excel and Statistica 6.0 using descriptive statistics. The frequency of cases of active CMV and EBV infection was calculated mathematically by the binomial coefficient of I. Newton. Research results and their discussion. We found in the vast majority of patients with SLE (117 patients, 97.50%) increase in the titer of specific antibodies to CMV. Only in 3 patients (2.50%) the titer of antibodies to this virus was within normal limits. Analyzing the frequency of EBV infection in patients with SLE, we recorded an increase in the titer of specific antibodies to the virus in 119 patients (99.17%). Among the examined patients with SLE in all (100.00%) found an increase in the titer of antibodies to CMV and / or EBV, of which 97.50% - infected with CMV and 97.17% - infected with EBV. The active phase of CMV and / or EBV infection was detected in 54.17%, of which 23.33% - active CMV infection, 17.50% - active EBV infection and 12.50% - a combination of active CMV and EBV infection simultaneously, which indicates a high frequency of CMV and EBV infection in patients with SLE and reflects the urgency of the problem of diagnosing herpesvirus infection in them. We found that activeCMV, EBV infections and their combinations are present only in women (64 patients, which is 60.96% of the total number of women with SLE), of which 28 patients (26.67%) there was only active CMV infection, in 21 patients (20.00%) - only active EBV infection and in 15 patients (14.29%) – combination of active CMV and EBV infection. 41 women (39.05%) and all (100.00%) men were not found to have active CMV and EBV infection, which indicates that men at the time of the survey were significantly more likely to have this infection in the integration phase. The most frequently active EBV infection was detected in patients with SLE of young age (17 cases, 24.64%), and in middle-aged patients 3 cases (6.52%) were recorded, which indicates a significant (p <0.05) difference in the frequency of cases of active EBV infection in patients of both groups. Only 1 case (20.00%) of active EBV infection was detected in elderly patients. Conclusions. All patients with systemic lupus erythematosus are infected - 97.50% with cytomegalovirus and 97.17% with Epstein-Barr virus infection, that was confirmed by the increased titer of antibodies to them. Among the mentioned patients 53.33% of them had the active phase of infection (23.33% - cytomegalovirus infection in the replication phase, 17.50% - the Epstein- Barr virus infection in the replication phase and 12.50% - their combination). The prevalence of active viral infection in patients with systemic lupus erythematosus depends on gender (active cytomegalovirus, active Epstein-Barr virus infection and their combination are significantly more common in women) and age - they are probably more common in young patients.  


2021 ◽  
pp. 549-554
Author(s):  
Berrin Pelit Uzunalimoğlu ◽  
Abdülhamit Sağlam ◽  
Büşra Şişman ◽  
Sefer Günaydın ◽  
Esen Gül Uzuner ◽  
...  

Epstein-Barr virus (EBV) has been associated with a plethora of neurological manifestations including polyneuropathy and polyradiculopathy. A 27-year-old man with a recent upper respiratory system infection presented with difficulty in walking. His neurological examination revealed reduced muscle strength in both proximal and distal lower limb muscles without sensory and autonomic signs. Needle electromyography showed abnormal spontaneous activity and reduced recruitment of motor units in muscles innervated by multiple lumbo-sacral roots. Cerebrospinal examination showed increased protein levels with normal cell counts. While spinal MRI was normal, whole-body CT and PET examination showed disseminated lymph node enlargement. Anti-EBV viral capsid antigen and anti-nuclear antigen IgG but not IgM was positive, whereas EBV PCR was negative in blood. Analysis of inguinal lymph node biopsy showed reactive lymphoid hyperplasia and EBV DNA. Leucine-rich glioma-inactivated protein 1 (LGI1) antibody was found in serum but not in CSF. All clinical, imaging, and electrophysiological findings improved following steroid and intravenous immunoglobulin treatment. These findings suggested the acute involvement of lumbo-sacral spinal roots and/or motor neurons. Purely motor polyradiculopathy has been reported in both EBV-positive and LGI1 antibody-positive patients, and EBV infection is known to precede different autoimmune manifestations. Whether EBV infection may trigger LGI1 autoimmunity and cause involvement of spinal motor roots and/or motor neurons needs to be further studied.


PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 964-967
Author(s):  
THOMAS J. BOWEN ◽  
RALPH J. WEDGWOOD ◽  
HANS D. OCHS ◽  
WERNER HENLE

In vivo and in vitro humoral and cellular immune responses were studied in a 2½-year-old girl immediately before, during, and after an asymptomatic infection with Epstein-Barr virus. During the acute EBV infection, the patient's peripheral blood mononuclear cells were deficient in immunoglobulin synthesis and suppressed the in vitro immunoglobulin synthesis of normal allogeneic cells. In vitro mitogen transformation of lymphocytes was reduced. In vivo antibody responses to the T cell-dependent antigens bacteriophage φX 174 and Keyhole limpet hemocyanin were markedly depressed. These studies suggest that suppressor cells induced during acute EBV infection not only suppress immunoglobulin synthesis in vitro, but also interfere with in vivo antibody synthesis.


Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1092-1095 ◽  
Author(s):  
A Neri ◽  
F Barriga ◽  
G Inghirami ◽  
DM Knowles ◽  
J Neequaye ◽  
...  

Abstract The Epstein-Barr virus (EBV) is associated with distinct forms of human lymphoid malignancies, including the endemic (eBL) and sporadic forms of Burkitt's lymphoma (sBL) and acquired immunodeficiency syndrome- associated non-Hodgkin lymphoma (AIDS-NHL). However, whether EBV has a pathogenetic role in these tumors or is a passenger virus has not been conclusively demonstrated. One element to distinguish between these two possibilities is to determine whether EBV infection has preceded and, thus, possibly contributed to clonal expansion, or whether infection has occurred after clonal expansion and thus is unlikely to contribute to pathogenesis. Toward this end we analyzed the structure of the heterogeneous genomic termini of EBV as markers of clonal infection in a panel of eBL (11 cases), sBL (9 cases), and AIDS-NHL (10 cases) biopsies. We show that EBV termini are uniformly clonal in sBL, eBL, and AIDS-NHL, strongly suggesting that EBV infection has preceded and, thus, most likely contributed to clonal expansion in these malignancies.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2722
Author(s):  
Fenggang Yu ◽  
Yanan Lu ◽  
Yingying Li ◽  
Yuji Uchio ◽  
Utomo Andi Pangnguriseng ◽  
...  

Epstein–Barr virus (EBV) is a human oncogenic virus that causes several types of tumor, such as Burkitt’s lymphoma and nasopharyngeal carcinoma (NPC). NPC tumor cells are clonal expansions of latently EBV-infected epithelial cells. However, the mechanisms by which EBV transforms the nasopharyngeal epithelium is hampered, because of the lack of good in vitro model to pursue oncogenic process. Our primary nasopharyngeal epithelial cell cultures developed pseudostratified epithelium at the air-liquid interface, which was susceptible to EBV infection. Using the highly sensitive RNA in situ hybridization technique, we detected viral infection in diverse cell types, including ciliated cells, goblet cells, and basal cells. EBV-encoded small RNA-positive cells were more frequently detected in the suprabasal layer than in the basal layer. We established the most physiologically relevant EBV infection model of nasopharyngeal epithelial cells. This model will advance our understanding of EBV pathogenesis in the development of NPC.


2002 ◽  
Vol 76 (18) ◽  
pp. 9420-9433 ◽  
Author(s):  
Julie L. Boyer ◽  
Sankar Swaminathan ◽  
Saul J. Silverstein

ABSTRACT The herpes simplex virus type 1 (HSV-1) ICP27 protein is an essential RNA-binding protein that shuttles between the nucleus and cytoplasm to increase the cytoplasmic accumulation of viral late mRNAs. ICP27 homologs have been identified in each of the herpesvirus subfamilies, and accumulating evidence indicates that homologs from the gammaherpesvirus subfamily function similarly to ICP27. In particular, the Epstein-Barr virus (EBV) SM protein posttranscriptionally regulates gene expression, binds RNA in vitro and in vivo, and shuttles between the nucleus and cytoplasm. To determine if these two proteins function through a common mechanism, the ability of EBV SM to complement the growth defect of an HSV-1 ICP27-null virus was examined in a transient-expression assay. ICP27 stimulated the growth of the null mutant more efficiently than did SM, but the ability of SM to compensate for the ICP27 defects suggests conservation of common functions. To assay for complementation in the context of a viral infection, the growth properties of an HSV recombinant expressing SM in an ICP27-null background were analyzed. SM stimulated growth of the recombinant, although this growth was reduced by comparison to that of an ICP27-expressing virus. By contrast, an HSV recombinant expressing an SM mutant allele defective for transactivation activity and nucleocytoplasmic shuttling did not grow at all. These results suggest that SM and ICP27 may regulate gene expression through a common pathway that is evolutionarily conserved in herpesviruses.


Author(s):  
Bert A. ‘t Hart

Abstract Using a non-human primate model of the autoimmune neuroinflammatory disease multiple sclerosis (MS), we have unraveled the role of B cells in the making and breaking of immune tolerance against central nervous system myelin. It is discussed here that B cells prevent the activation of strongly pathogenic T cells present in the naïve repertoire, which are directed against the immunodominant myelin antigen MOG (myelin oligodendrocyte glycoprotein). Prevention occurs via destructive processing of a critical epitope (MOG34-56) through the lysosomal serine protease cathepsin G. This effective tolerance mechanism is abrogated when the B cells are infected with Epstein–Barr virus, a ubiquitous γ1-herpesvirus that entails the strongest non-genetic risk factor for MS.


2017 ◽  
Vol 145 (16) ◽  
pp. 3405-3412 ◽  
Author(s):  
V. GARES ◽  
L. PANICO ◽  
R. CASTAGNE ◽  
C. DELPIERRE ◽  
M. KELLY-IRVING

SUMMARYEpstein-Barr virus (EBV) is a highly prevalent herpesvirus linked to infectious mononucleosis and several malignancies. This paper aims to study the association between children's early life social environment at 9 months and EBV infection at 3 years of age.MethodsWe used data on children included in the UK Millennium Cohort Study. We described the social environment using area-level and material factors as well as socioeconomic position (SEP) at 9 months. EBV was measured at 3 years of age (n = 12 457).ResultsLower rates of EBV infection were observed in children living in towns and rural areas compared with those living in cities. Lower SEP and overcrowding in the household increased the odds of being infected. Children whose parents were social tenants were more likely to be infected than homeowners. In the overall model, the strength of the association between material factors and EBV infection weakened.ConclusionsWe showed that early life material deprivation was associated with a higher risk of EBV infection among 3-year-olds. Children living in more deprived social conditions may be more likely to become EBV carriers at an earlier age.


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