Molecular Epidemiology and Genetic Diversity of Epstein - Barr virus among lymphoma patients in Ethiopia
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Date
2024-06-13
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Addis Ababa University
Abstract
Background: The Epstein-Barr virus (EBV) is a member of the herpesvirus family and is highly prevalent among the global population. It is estimated that more than 90% of adults have been exposed to this virus, making it one of the most common human viruses worldwide. After initial infection, infectious mononucleosis (IM), which typically occurs during childhood or adolescence, EBV establishes a long-lasting latent infection within B lymphocytes. EBV is associated with various diseases such as Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, and certain types of Gastric cancer. Studying the overall viral molecular epidemiology and genetic diversity of EBV can provide valuable insights into the pathogenesis, diagnosis, and management of EBV-associated diseases. The objectives of the study were on various aspects of EBV among lymphoma patients. It encompasses the detection of EBV, determining the genotypes, analysis of its methylation status, and identification of sequence variations.
Methods: The study was conducted at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, spanning from June 2021 to August 2023. A total of 305 participants were enrolled retrospectively and prospectively, and formalin-fixed paraffin-embedded (FFPE) tissues, blood, and lymph node biopsy samples were collected. From the whole blood samples, serum plasma and polymorphonuclear blood mononuclear cells (PBMCs) were isolated. Additionally, lymphomononuclear cells (LMNCs) were isolated from the lymph node biopsy samples. DNA was extracted from FFPE samples, PBMCs, and LMNCs. Serological tests were conducted using Viral capsid antigen (VCA) IgG to detect antibodies, and molecular detection and quantification were carried out using quantitative PCR (qPCR) by targeting EBV EBNA1 gene. Genotyping was performed using conventional PCR targeting the EBNA3C gene. The viral methylation profile was assessed using the IPLEX assay, and sequencing of the viral genome was performed using next generation sequencing technology (Illumina). We utilized statistical analysis tools such as descriptive statistics (mean, median, frequencies, percentages) and employed techniques like chi square test, bioinformatics, and phylogenetic tree analysis for in-depth data examination. SD, 17.5).
Results: The mean age of the study participants was 38 years ( Among the lymphoma patients in the study, 32% (n=91) were diagnosed with Hodgkin lymphoma, while the remaining (68%) patients had non-Hodgkin lymphoma (n=197). Within the non-Hodgkin lymphoma cases, the highest percentage (18%) was attributed to small lymphocytic lymphoma, followed by diffuse
Conclusion: This study presents the first evidence-based data in Ethiopia, providing valuable insights into the epidemiology and virological characteristics of lymphoma patients with EBV infection. These findings significantly contribute to our understanding of the relationship between EBV and lymphoma, emphasizing the importance of viral load, genotyping, methylation status, and genetic variations in different EBV genotypes. However, further research across diverse populations is necessary to broaden our knowledge of this complex virus and its association with lymphoma development. Such knowledge holds great potential for the development of region specific diagnostic and therapeutic strategies targeting EBV-associated lymphoma.
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Molecular Epidemiology and Genetic