Association of Human Papilloma Virus, Cytomegalovirus, and Epstein-Barr Virus with Breast Cancer in Jordanian Women.

Background and Objectives: The investigation of oncogenic viruses and their potential association with breast cancer (BC) remains an intriguing area of study. The current work aims to assess evidence of three specific viruses, human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in BC samples and to explore their relationship with relevant clinicopathological variables. Materials and Methods: The analysis involved BC samples from 110 Jordanian female patients diagnosed with BC and breast tissue samples from 30 control patients with no evidence of breast malignancy, investigated using real-time PCR. The findings were then correlated with various clinico-pathological characteristics of BC. Results: HPV was detected in 27 (24.5%), CMV in 15 (13.6%), and EBV in 18 (16.4%) BC patients. None of the control samples was positive for HPV or CMV while EBV was detected in only one (3.3%) sample. While (HPV/EBV), (HPV/CMV), and (EBV/CMV) co-infections were reported in 1.8%, 2.7%, and 5.5%, respectively, coinfection with the three viruses (HPV/CMV/EBV) was not reported in our cohort. A statistically significant association was observed between HPV status and age (p = 0.047), and between clinical stage and CMV infection (p = 0.015). Conclusions: Our findings indicate the presence or co-presence of HPV, CMV, and EBV in the BC subpopulation, suggesting a potential role in its development and/or progression. Further investigation is required to elucidate the underlying mechanisms that account for the exact role of oncoviruses in breast carcinogenesis.

EBV-Associated Gastric Cancer; An In Situ Hybridization Assay on Tissue Microarray: A Multi-Region Study from Four Major Provinces of Iran.

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran. METHODS: Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics. RESULTS: Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075). CONCLUSION: EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States.

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

The Prevalence of Epstein-Barr Virus in Normal, Premalignant, and Malignant Uterine Cervical Samples in Iran.

INTRODUCTION: It is suggested that Epstein-Barr virus (EBV) may play an important role in cervical cancer development. Most studies found a higher rate of EBV in cervical cancer samples in comparison to premalignant and normal groups. In this regard, this study aimed to investigate the prevalence of EBV in cervical samples. METHODS: In total, 364 samples from 179 healthy subjects, 124 women with premalignant lesions, and 61 patients with cervical cancer were investigated using nested-PCR. RESULTS: The mean age ± SE was 54.1 ± 13.4 in women with cervical cancer, 36.1 ± 9.4 among women with premalignant lesions, and 36.6 ± 11.5 in healthy individuals. In total, 290 out of 364 samples were human papillomavirus (HPV) positive and the following HPV genotypes were detected among them: HPV 16/18 was found in 43.1%, 23.9%, and 65.5% of normal, premalignant, and malignant samples, respectively, and other high-risk types were detected in 56.9% of normal, 76.1% of premalignant, and 34.5% of malignant samples. The prevalence of EBV was found to be 9.8%, 2.4%, and 2.8% in cervical cancer, premalignant lesions, and normal specimens, respectively, and the difference was statistically significant (p = 0.028). The overall frequency of coinfection between EBV and HPV was shown to be 3.6%. The coinfection was more prevalent among HPV 16/18-infected samples than other high-risk HPVs (6.6 vs. 2.9%) although the difference was not reached a statistically significant difference (p = 0.23). CONCLUSION: Our findings indicated that EBV could play an important role as a cofactor in the progression of cervical cancer. However, future studies with larger sample sizes and the expression analysis of EBV transcripts or proteins are mandatory.

Epstein-Barr virus reactivation and disease flare of systemic lupus erythematosus.

SLE affects females rather than males with a ratio of about 9:1. Owing to the high morbidity with multiple organ involvement, SLE flare-up remains a challenge for women's health. In an accumulation of the past 70 years of studies globally, EBV has been found to be strongly associated with SLE. In the past two decades, EBV reactivation has been proven as prevalent in SLE patients as well as being strongly associated with higher SLE activity and higher prevalence of SLE flare. Hence, strategies to control EBV reactivation in SLE including pharmacological (such as Tenofovir prodrugs TDF and TAF) and non-pharmacological approaches are being developed. The heterogeneity of SLE constitutes clinical challenges, suggesting a stratification of SLE into subgroups based on EBV reactivation or non-reactivation is reasonable. Future-wise, adding anti-EBV reactivation medication to current immunosuppressants for the subgroup of SLE patients with EBV reactivation could be beneficial to achieve long-term remission of SLE.

Time trends in herpesvirus seroepidemiology among Swedish adults.

BACKGROUND: Human herpesviruses are widespread among the human population. The infections often occur unnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence varies among subpopulations and with time. The aim of this study was to describe the seroprevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish population over a time period of several decades. METHODS: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old men and 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibodies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linear regression analysis was used to differentiate between other factors such as age and gender. RESULTS: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1 and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus (p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the prevalence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women, and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011). CONCLUSIONS: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virus decreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a child and adolescent.

Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

PURPOSE: Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. METHODS: In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. RESULTS: The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. CONCLUSION: While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.

Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by the gain of function of the CXCR4 chemokine receptor. We present the prevalence of cancer in WHIMS patients based on data from the French Severe Chronic Neutropenia Registry and an exhaustive literature review. The median follow-up of the 14 WHIMS 'patients was 28.5 years. A central review and viral evaluation of pathological samples were organized, and we conducted a thorough literature review to identify all reports of WHIMS cases. Six French patients were diagnosed with cancer at a median age of 37.6 years. The 40-year risk of malignancy was 39% (95% confidence interval [CI]: 6%-74%). We observed two human papillomavirus (HPV)-induced vulvar carcinomas, three lymphomas (two Epstein-Barr virus [EBV]-related) and one basal cell carcinoma. Among the 155 WHIMS cases from the literature, 22 cancers were reported in 16 patients, with an overall cancer 40-year risk of 23% (95% CI: 13%-39%). Malignancies included EBV-associated lymphoproliferative disorders and HPV-positive genital and anal cancers as in the French cohort. Worldwide, nine cases of malignancy were associated with HPV and four with EBV. Immunocompromised WHIMS patients appear to be particularly susceptible to developing early malignancy, mainly HPV-induced carcinomas, followed by EBV-related lymphomas.

The Level of Anti-Viral Antigen-Specific Antibodies to EBNA-1 in the Serum of MS Patients Does not Depend on the Severity of the Disease.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease leading to inevitable disability and primarily affecting the young and middle-aged population. Recent studies have shown a direct correlation between the risk of MS development and Epstein-Barr virus (EBV) infection. Analysis of the titer of EBV-specific antibodies among patients with MS and healthy donors among Russian population confirmed that MS is characterized by an increased level of serum IgG binding EBNA-1 (EBV nuclear antigen 1). The number of patients with elevated levels of EBNA-1-specific antibodies does not differ statistically significantly between two groups with diametrically opposite courses of MS: benign MS or highly active MS. It can be assumed that the primary link between EBV and the development of MS is restricted to the initiation of the disease and does not impact its severity.

Epstein-Barr virus seroprevalence among inflammatory bowel disease patients in Saudi Arabia.

BACKGROUND: Seroprevalence of Epstein-Barr virus (EBV) in patients with inflammatory bowel disease (IBD) is variable based on geographic distribution. There are no published data on the seroprevalence of EBV in patients with IBD in Saudi Arabia. This study aims to assess the seroprevalence of EBV in patients with IBD in a tertiary center in Saudi Arabia. METHODS: This is a retrospective chart review of patients ≥14 years of age with a confirmed diagnosis of IBD and known EBV status at our institution from January 1, 2018, to January 1, 2023. The primary outcome was the seroprevalence of EBV in IBD. Secondary outcomes included factors associated with EBV seropositivity and rates of EBV seroconversion in originally negative patients. RESULTS: A total of 150 patients were included (74.7% with Crohn's disease, median age 28 years [interquartile range 21-36.3]). EBV non-exposure was noted in 16.8% ( n = 25). The mean age was significantly lower in the EBV-naïve group at 26 ± 8.5 years compared to the EBV-exposed group at 31.2 ± 12.9 years ( P = 0.02). Seroprevalence of EBV was highest in patients >40 years of age (92.9%) and lowest in patients 14-25 years of age (78.2%). The rate of seroconversion in EBV-naïve patients was 16.7% after a mean follow-up time of 47.9 ± 46.3 months. CONCLUSION: In our cohort of IBD patients, 16.8% were naïve to EBV, and young age was a significant predictor of EBV non-exposure. Our data supports the practice of assessing EBV before initiating thiopurine therapy since EBV seroprevalence is not universal in our population.

Diabetes can increase the prevalence of EBV infection and worsen the prognosis of nasopharyngeal carcinoma.

Epstein‒Barr virus (EBV) infection is a primary oncogenic factor of nasopharyngeal carcinoma (NPC) that elicits epithelial-mesenchymal transition (EMT). Although diabetic patients are more susceptible to various infectious diseases, the pathological association with virus-related NPC has not yet been clarified. Herein, we evaluated the influence of diabetes on the clinicopathological changes of 70 patients with NPC. Disease-specific survival (DSS) modified by viral infection was also analysed. The proportion of NPC patients with diabetes was 32.9% (23/70 cases), and 91.3% (21/23 cases) were infected with EBV detected by EBER-I in situ hybridisation. NPC with diabetes showed an effect on EMT evaluated by immunostaining for E-cadherin and vimentin, which was correlated with HbA1c levels. Receiver operating characteristic (ROC) curve analysis determined a HbA1c level of 6.5% as the cut-off value for primary disease death at 2 years [area under the curve (AUC) 0.76; sensitivity 0.64; and specificity 0.81]. High HbA1c levels (≥6.5%) significantly increased the number of lymph node metastases in NPC compared to low HbA1c levels (<6.5%, p<0.01). Diabetic NPC patients had a significantly poorer prognosis than all non-diabetic patients (DSS, 72 months vs not reached, p<0.05). Diabetic EBV-positive NPC patients had a significantly poorer prognosis than non-diabetic EBV-positive patients (DSS, 35 months vs not reached, p<0.01). Multivariate analysis using the Cox proportional hazards model also suggested that HbA1c ≥6.5% was a significant factor in poor prognosis, with a hazard ratio of 6.84 (p<0.05). Collectively, our results revealed for the first time a high prevalence of EBV infection, poor prognosis and the importance of proper glycaemic control in diabetic NPC patients.

The association between various viral infections and multiple sclerosis: An umbrella review on systematic review and meta-analysis.

Multiple Sclerosis (MS) is one of the immune-mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the pathogenesis of MS. Also, it can be said that infections are a key component of the host's response to MS development. Finally, we evaluated the relationship between different pathogens and MS disease in this umbrella research. We systematically collected and analysed multiple meta-analyses focused on one particular topic. We utilised the Scopus, PubMed, and Web of Science databases starting with inception until 30 May 2023. The methodological quality of the analysed meta-analysis has been determined based on Assessing the Methodological Quality of Systematic Reviews 2 and Grade, and graph construction and statistical analysis were conducted using Comprehensive Meta-Analysis. The Confidence Interval of effect size was 95% in meta-analyses, and p < 0.05 indicated a statistically meaningful relationship. The included studies evaluated the association between MS and 12 viruses containing SARS-CoV-2, Epstein-Barr virus (EBV), Hepatitis B virus, varicella-zoster virus (VZV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, HSV-1, HSV-2, Cytomegalovirus, Human Papillomavirus, and influenza. SARS-CoV-2, with a 3.74 odds ratio, has a significantly more potent negative effect on MS among viral infections. After that, EBV, HHV-6, HSV-2, and VZV, respectively, with 3.33, 2.81, 1.76, and 1.72 odds ratios, had a significantly negative relationship with MS (p < 0.05). Although the theoretical evidence mostly indicates that EBV has the greatest effect on MS, recent epidemiological studies have challenged this conclusion and put forward possibilities that SARS-CoV-2 is the culprit. Hence, it was necessary to investigate the effects of SARS-CoV-2 and EBV on MS.

Molecular profile of gastric adenocarcinoma, relevant epidemiological factors - Systematic review and meta-analysis relating sex with Epstein-Barr virus and unstable microsatellites subtypes.

INTRODUCTION: Gastric epithelial tumors exhibit morphological heterogeneity, diverse biological behaviors, and different oncopathological pathways. The Cancer Genome Atlas (TCGA) proposed a molecular classification of gastric adenocarcinomas based on genetic and molecular findings, which shows particular characteristics of diagnosis, prognosis, and indirectly, therapeutic alternatives. Within this classification, Epstein-Barr virus-positive (EBV+) and high microsatellite instability (MSI-H) subtypes stand out as subtypes that present a less aggressive biological behavior and a highly mutilated phenotype. This study conducted a systematic review with an emphasis on epidemiological and prognostic factors based on the molecular classification proposed by TCGA. METHODS: A broad, comprehensive, and reproducible search with methodological rigor was conducted for study selection using the ROBINS-I and GRADEpro protocols and appropriate combinations of keywords. RESULTS: A total of 25 studies were selected: six with a complete classification similar to TCGA and 19 with a distinction between MSI-H and EBV+. The application of meta-analysis calculations reinforces the prevalence of positive Epstein-Barr adenocarcinomas in males and high microsatellite instability in females, with a high level of certainty of evidence and low risk of bias in the analyzed studies due to the rigorous methods used. CONCLUSION: The molecular classification proposed by TCGA shows limited dissemination, with MSI-H and EBV+ subtypes being the most researched, probably due to the benefit of the association with immunotherapies. However, the subclassification cannot be restricted to less than a quarter of the cases, and improvements in this aspect are urgent for the construction of knowledge on this important topic of global health.

Tumor molecular landscape of Epstein-Barr virus (EBV) related nasopharyngeal carcinoma in EBV-endemic and non-endemic areas: Implications for improving treatment modalities.

Epstein-Barr virus (EBV) related- nasopharyngeal carcinoma (NPC) is a squamous carcinoma of the nasopharyngeal mucosal lining. Endemic areas (EA) are east and Southeast Asia, were NPC was recorded with higher incidence and longer estimated survival than in non-endemic area (NEA) such as Europe, We analyzed the gene expression and microenvironment properties of NPC in both areas to identify molecular subtypes and assess biological and clinical correlates that might explain the differences in incidence and outcome between EA- and NEA-NPCs. Six EA-NPC transcriptomic datasets, including tumor and normal samples, were integrated in a meta-analysis to identify molecular subtypes using a ConsensusClusterPlus bioinformatic approach. Based on the biological/functional characterization of four identified clusters were identified: Cl1, Immune-active; Cl2, defense-response; Cl3, proliferation; Cl4, perineural-interaction/EBV-exhaustion. Kaplan-Meier survival analysis, applied to the single dataset with available disease-free survival indicated Cl3 as the cluster with the worst prognosis (P = 0.0476), confirmed when applying four previously published prognostic signatures. A Cl3 classifier signature was generated and its prognostic performance was confirmed (P = 0.0368) on a validation dataset. Prediction of treatment response suggested better responses to: radiotherapy and immune checkpoint inhibitors immune-active and defense-response clusters; chemotherapy proliferation cluster; cisplatin perineural-interaction/EBV-exhaustion cluster. RNA sequencing for gene expression profiling was performed on 50 NEA-NPC Italian samples. In the NEA cohort, Cl1, Cl2 and Cl3 were represented, while perineural-interaction/EBV-exhaustion was almost absent. The immune/biological characterization and treatment-response prediction analyses of NEA-NPC partially replicated the EA-NPC results. Well characterized EA- and NEA-NPC retrospective and prospective cohorts are needed to validate the obtained results and can help designing future clinical studies.

Prevalence, management, and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HCT: survey of Infectious Diseases Working Party EBMT.

The aim of this study was to determine the current approach of EBV-driven post-transplant complications in context of monitoring, diagnosis, prevalence and treatment in EBMT transplant centers. Routine serology testing in patient and donor before HCT is performed in 95.5% centers. Pretransplant EBV-DNA is routinely tested in all patients in 32.7% centers. Monitoring for EBV infection is feasible in 98.2% centers: including 66.7% centers using standardized PCR. Post-HCT regular monitoring is performed in all patients in 80.5% centers. Anti-EBV prophylaxis with rituximab is used in 12.4% centers. Frequency of csEBV-DNA-emia was 7.4% (adults: 6.2%, children: 12.6%). The PCR threshold used to start preemptive treatment was differentiated among centers. Frequency of EBV-PTLD was 1.6% (adults: 1.3%; children: 3.5%). First-line therapy of EBV-driven complications was rituximab and reduction of immunosuppressive therapy. The rate of failure of first-line preemptive treatment was 12.0%. EBV-specific viral-specific T-lymphocytes were available in 46.0% centers. A number of new experimental therapies were given in 28 patients with resistant/refractory PTLD. In conclusion, the prevalence of EBV-DNA-emia and EBV-PTLD over the period 2020-2021 decreased in comparison to historical data. New trends (routine pretransplant screening for EBV-DNA, wider access to VST, new experimental therapies) are being observed in management of EBV infection after allo-HCT.

Post-transplant lymphoproliferative disorder in pediatric liver transplant recipients: Experience from a South African transplant center.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a clinically heterogeneous potentially fatal complication of pediatric liver transplantation (PLT). We determined the prevalence, complications, and associated factors for PTLD in PLT recipients from Wits Donald Gordon Medical Centre, South Africa from January 2012 to August 2019. METHODS: We performed a retrospective record review of 150 PLT recipients. RESULTS: Histologically proven PTLD occurred in 17/150 PLT recipients (11.3%). Children with PTLD were significantly younger at transplant (17.9 vs. 32.7 months, p = 0.001) with a significantly higher prevalence of obstructive etiology (17/17 vs. 81/133, p = 0.001). Fifteen (88.2%) children with PTLD were Epstein-Barr virus (EBV) seronegative at transplant. High post-transplant EBV viral load at a threshold value of 4.8 log10 DNA copies/mL (sensitivity: 80.0% [95% confidence interval {CI}, 46.7%-100.0%]; specificity: 73.1% [95% CI 42.3%-93.3%; area under the curve {AUC} 75.8%]) and low post-transplant albumin levels at a threshold value of 21.5 g/L (sensitivity: 70.6% [95% CI, 41.2%-94.1%]; specificity: 85.7% [95% CI, 60.4%-94.5%; {AUC} 74.8%]) were associated with PTLD. The prevalence of cytomegalovirus (CMV) disease was significantly higher in children who developed PTLD versus non-PTLD (12/17 vs. 18/133; p < 0.001). CMV disease and the combination of post-transplant high EBV viral load and low albumin were independently associated with an increased risk of developing PTLD. Four (23.5%) children with PTLD died, however, survival was equivalent to non-PTLD PLT (p = 0.580). CONCLUSION: The prevalence of PTLD in our cohort mirrors international cohorts, with mortality similar to non-PTLD PLT recipients.

Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus.

Frequency and association of Epstein-Barr Virus genotype in rheumatoid arthritis patients of Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Rheumatoid arthritis (RA) is an immune-mediated, polyarthritis linked with various genetic and environmental causative agents. Among environmental triggers, Epstein-Barr Virus (EBV) is considered the most potent etiological agent. OBJECTIVE: This study aimed to investigate the prevalence of EBV and its genotypes in RA patients and to investigate their association with clinical and laboratory parameters of RA. METHODOLOGY: This study included blood samples of RA and control healthy individuals (100 each). Blood samples along with clinical and laboratory parameters were collected from patients after consent in the Department of Rheumatology, at Lady Reading Hospital, in Peshawar Pakistan. Blood samples were processed for DNA extraction followed by PCR amplification for EBV detection and genotype discrimination. RESULTS: RA patients were 85 females and 15 males with a mean age of 40.13±14.05 years. EBV Type-1 was detected in 45% of RA and 9% of control cases. The mean disease duration of RA patients was 6.61±6.23 years. Out of 100 diseased patients, 43% were seropositive rheumatoid arthritis (SPRA) and showed a significant correlation with a family history of RA in EBV-positive individuals (P = 0.017). The demographic, clinical, and laboratory parameters of RA patients showed a non-significant association with EBV. Moreover, only a family history and Serum creatinine of RA patients showed a significant association with EBV (P = 0.0001 and P = 0.022 respectively). CONCLUSION: It is concluded that EBV-1 is prevalent and associated with RA. Further investigation is required for detailed genetic analysis of EBV to determine its possible role in modulating the immune system in RA.

Characteristics of self-regulation of the epidemic process of infection caused by the Epstein-Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4).

INTRODUCTION: Among the available scientific literature, there are no publications addressing processes of self-regulation in the parasite-host population systems with reference to chronic infections, including the infection caused by the Epstein-Barr virus (EBV infection). The aim of the study is to assess manifestations of the epidemic process of chronic EBV infection through the lens of the basic tenets of the theory of self-regulation of parasitic systems. MATERIALS AND METHODS: The study was performed using data from scientific publications selected from such database sources as Scopus, Web of Science, Cochrane Library, PubMed, CyberLeninka, RSCI, etc. The list of analyzed publications included published articles of the authors of this study, reporting the results of the retrospective epidemiological analysis of the incidence of infectious mononucleosis in Russia in general and in Moscow in particular, as well as the results of the laboratory tests regarding the detection frequency of specific antibodies to EBV proteins. RESULTS: The chronic course of EBV infection promotes a close long-term interaction between the pathogen and the host. The genetic variability of the pathogen and the functions of specific and nonspecific human immune defense systems play a key role in the interaction between two heterogeneous populations and underlie their phasal self-transformation. A variety of social and natural factors (adverse chemical, physical, biological, climatic impacts, etc.) trigger the reactivation of chronic EBV infection, thus providing the continuous existence of additional sources of infection in the host population. CONCLUSION: The analysis of the manifestations of chronic EBV infection in the context of the theory of self-regulation of parasitic systems promotes the understanding of the factors underlying the unevenness of its epidemic process. The obtained data can be adjusted for other infections having similar transmission mechanisms and virus life cycles (including other herpes infections) to map out strategies to control the epidemic process of chronic infections spread by aerosol transmission of the pathogen.

[Herpes viruses and human papillomavirus in prostate cancer: first results].

INTRODUCTION: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are among the most common urological diseases in men. It has been repeatedly suggested that viral infection plays an important role in prostate carcinogenesis. AIM: To assess the relationship between viral infection and PCa, as well as the clinical and morphological features of BPH and PCa. MATERIALS AND METHODS: A total of 98 patients undergoing treatment for BPH (n=48) or PCa (n=50) between 2019 and 2021 were included in the study. Real-time PCR on the surgical specimens for human papillomaviruses (HPV), herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes virus type 6 (HSV-6) was performed. RESULTS: In patients with PCa, viruses in prostate tissue were found more often compared to those with BPH (50.0 vs. 31.3%, respectively, p=0.046.) The most common virus in both PCa and BPH was EBV (22.0 vs. 16.7%, respectively). The second most common virus in patients with PCa was HSV-6 (20.0%), which was not detected in any men with BPH (p=0.003). There was a trend toward higher prevalence of CMV among patients with PCa (16.0% vs. 4.2%), but the difference was not significant (p=0.09). There was no association of viral infection with clinical and morphological features. CONCLUSIONS: The resulting trend toward a higher prevalence of HSV-6 and CMV in patients with PCa compared to those with BPH creates the prerequisites for further study of viruses in prostate diseases involving a larger cohort, which will provide an idea of the multi-stage process of malignant transformation and, possibly, open new therapeutic options for prevention and treatment.