Genomic Landscapes of Epstein-Barr Virus in Pulmonary Lymphoepithelioma-like Carcinoma

2021 ◽  
Author(s):  
Yan-Xia Wu ◽  
Wen-Li Zhang ◽  
Tong-Min Wang ◽  
Ying Liao ◽  
Yi-Jun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epstein Barr Virus ◽  
Primary Lung Cancer ◽  
Genome Wide Association ◽  
Healthy Controls ◽  
Barr Virus ◽  
Ebv Infection ◽  
Genome Wide ◽  
Mutational Hotspots ◽  
Epstein Barr

Epstein-Barr virus (EBV) infection is associated with multiple malignancies, including pulmonary lymphoepithelioma-like carcinoma (pLELC), a particular subtype of primary lung cancer. However, the genomic characteristics of EBV related to pLELC remain unclear. Here, we obtained the whole-genome dataset of EBV isolated from 78 pLELC patients and 37 healthy controls using EBV-captured sequencing. Compared to the reference genome (NC_007605), a total of 3995 variations were detected across pLELC-derived EBV sequences, with the mutational hotspots located in latent genes. Combined with 180 published EBV sequences derived from healthy people in Southern China, we performed a genome-wide association study and identified 32 variations significantly related to pLELC ( p < 2.56×10 −05 , Bonferroni correction), with the top signal of SNP coordinate T7327C (OR = 1.22, p = 2.39×10 −15 ) locating in the origin of plasmid replication (OriP). The results of population structure analysis of EBV isolates in East Asian showed the EBV strains derived from pLELC were more similar to those from nasopharyngeal carcinoma (NPC) than other EBV-associated diseases. In addition, typical latency type-II infection were recognized for EBV of pLELC at both transcription and methylation levels. Taken together, we defined the global view of EBV genomic profiles in pLELC patients for the first time, providing new insights to deepening our understanding of this rare EBV-associated primary lung carcinoma. Importance Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rarely distinctive subtype of primary lung cancer closely associated with Epstein-Barr virus (EBV) infection. Here, we gave the first overview of pLELC-derived EBV at the level of genome, methylation and transcription. We obtained the EBV sequences dataset from 78 primary pLELC patients, and revealed the sequences diversity across EBV genome and detected variability in known immune epitopes. Genome-wide association analysis combining 217 healthy controls identifies significant variations related to the risk of pLELC. Meanwhile, we characterized the integration landscapes of EBV at the genome-wide level. These results provided new insight for understanding EBV’s role in pLELC tumorigenesis.

scholarly journals Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

2019 ◽  
Author(s):  
Yasin Kaymaz ◽  
Cliff I. Oduor ◽  
Ozkan Aydemir ◽  
Micah A. Luftig ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
Population Structure ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Wide Association ◽  
Viral Dna ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71,P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.Key PointsEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.Genome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.Analysis of population structure reveals that EBV type 2 exists as two genomic sub groups.

scholarly journals Primary Lung Cancer Complicated by Malignant Lymphoma in Two Cases of Epstein-Barr Virus Infection

2012 ◽  
Vol 5 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Zentaro Ohno ◽  
Hidetoshi Tamaki ◽  
Takeshi Ohsuga ◽  
Hiroyuki Iwata ◽  
Norio Yasuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Virus Infection ◽  
Malignant Lymphoma ◽  
Epstein Barr Virus ◽  
Primary Lung Cancer ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

scholarly journals Association between Antibody Responses to Epstein-Barr Virus Glycoproteins, Neutralization of Infectivity, and the Risk of Nasopharyngeal Carcinoma

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Qian-Ying Zhu ◽  
Xiang-Wei Kong ◽  
Cong Sun ◽  
Shang-Hang Xie ◽  
Allan Hildesheim ◽  
...  
Keyword(s):  
Immune Response ◽  
Nasopharyngeal Carcinoma ◽  
Humoral Immune Response ◽  
Epstein Barr Virus ◽  
Healthy Controls ◽  
Humoral Immune ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Antibody Levels

ABSTRACT While Epstein-Barr virus (EBV) is the major cause of nasopharyngeal carcinoma (NPC), the value of the humoral immune response to EBV glycoproteins and NPC development remains unclear. Correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC requires systematic study. Here, we applied a cytometry-based method and enzyme-linked immunosorbent assay to measure neutralization of infectivity and antibody response to EBV glycoproteins (gH/gL, gB, gp350, and gp42) of plasma samples from 20 NPC cases and 20 high-risk and 20 low-risk healthy controls nested within a screening cohort in Sihui, southern China. We found that NPC cases have similar plasma neutralizing activity in both B cells and epithelial cells and EBV glycoprotein-specific IgA and IgG antibody levels compared with those of healthy controls. Significant correlations were observed between gH/gL IgG and gB IgG and the neutralizing ability against EBV infection of epithelial cells and B cells. These results indicate that a high level of glycoprotein antibodies may favor protection against primary EBV infection, instead of being low-risk biomarkers for NPC in long-term EBV-infected adults. In conclusion, this study provides novel insights into the humoral immune response to EBV infection and NPC development, providing valuable leads for future research that is important for prevention and treatment of EBV-related diseases. IMPORTANCE Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet. Therefore, EBV remains a major public health concern. To facilitate novel vaccines and therapeutics for NPC, it is of great importance to explore the impact of humoral immune response to EBV glycoproteins before the development of NPC. Therefore, in this study, we systematically assessed the correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC development. These results provide valuable information that will contribute to designing effective prevention and treatment strategies for EBV-related diseases such as NPC.

scholarly journals Epstein-Barr Virus Genomes Reveal Population Structure and Type 1 Association with Endemic Burkitt Lymphoma

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Yasin Kaymaz ◽  
Cliff I. Oduor ◽  
Ozkan Aydemir ◽  
Micah A. Luftig ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
Population Structure ◽  
Epstein Barr Virus ◽  
Genome Wide Association ◽  
Viral Dna ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr ◽  
Enrichment Methods

ABSTRACT Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is distinguished by its inclusion of Epstein-Barr virus (EBV). In order to better understand the impact of EBV variation in eBL tumorigenesis, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (n = 58) and healthy controls (n = 40) residing in the same geographic region in Kenya. Using our unbiased methods, we found that EBV type 1 was significantly more prevalent in eBL patients (74.5%) than in healthy children (47.5%) (odds ratio = 3.24, 95% confidence interval = 1.36 to 7.71, P = 0.007), as opposed to similar proportions in both groups. Controlling for EBV type, we also performed a genome-wide association study identifying six nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. In addition, viruses isolated from plasma of eBL patients were identical to their tumor counterparts consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions, as well as one novel genome with a 20-kb deletion, resulting in the loss of multiple lytic and virion genes. Comparing EBV types, viral genes displayed differential variation rates as type 1 appeared to be more divergent, while type 2 demonstrated novel substructures. Overall, our findings highlight the complexities of the EBV population structure and provide new insight into viral variation, potentially deepening our understanding of eBL oncogenesis. IMPORTANCE Improved viral enrichment methods conclusively demonstrate EBV type 1 to be more prevalent in eBL patients than in geographically matched healthy controls, which previously underrepresented the prevalence of EBV type 2. Genome-wide association analysis between cases and controls identifies six eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes. Analysis of population structure reveals that EBV type 2 exists as two genomic subgroups and was more commonly found in female than in male eBL patients.

scholarly journals Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein–Barr Virus Status–Defined Subgroups

2012 ◽  
Vol 104 (3) ◽  
pp. 240-253 ◽  
Author(s):  
Kevin Y. Urayama ◽  
Ruth F. Jarrett ◽  
Henrik Hjalgrim ◽  
Arjan Diepstra ◽  
Yoichiro Kamatani ◽  
...  
Keyword(s):  
Association Study ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

Relation between Epstein-Barr virus infection and Multiple Sclerosis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Aisha Yassin Abdul-Ghaffar ◽  
Dalia Youssef Samaha ◽  
Nancy Samir Wahba ◽  
Ahmed Essam Ali Hussein
Keyword(s):  
Multiple Sclerosis ◽  
Epstein Barr Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Epstein Barr Virus Infection ◽  
Healthy Controls ◽  
University Hospitals ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Abstract Background Multiple sclerosis (MS) is an immune mediated inflammatory disease that attacks myelinated axons in the central nervous system (CNS), destroying the myelin and the axon in variable degrees. The aetiology and pathogenesis of MS is complex and multifactorial, involving many interlacing mechanisms. Many theories had considered viral infections as a possible cause of MS. One of these viruses is Epstein-Barr virus (EBV), a herpes virus belonging to the family herpesviridae. There is obvious similarity between EBV and MS regarding their epidemiological pictures, and it was observed that most MS patients had a history of infectious mononucleosis (IM) a few years before onset. The relation between EBV and MS may give hope for development of biomarkers for prediction of disease development, early diagnosis, prediction of prognosis, curing or even preventing MS through an anti EBV vaccine or antiviral therapies. Objectives This study aims to analyze the association between EBV infection and multiple sclerosis. Subjects and Methods This is a case control study carried in the MS outpatient clinic at Ain Shams University Hospitals during the period from April 2019 till November 2019. Subjects included in this study were classified into two groups. The first group included 30 patients diagnosed as having MS, on the basis of their MRI finding, clinical presentation and according to revised Mc Donald criteria 2017. The patient group included 11 males and 19 females, their age ranged from 18 to 48 years. The second group included 30 age and sex matched healthy controls without any neurological or medical diseases. The control group included 11 males and 19 females, their age ranged from 18 to 48 years. Both groups were tested quantitatively for immunoglobulin G against Epstein Barr viral capsid antigen (VCA) using the enzyme linked immunosorbent assay technique (ELISA). Results All patients with MS (100%) were positive for EBV VCA IgG, whereas (93.33%) of controls were positive. In the MS group, the EBV VCA IgG mean level was (161± 66.32) U/ml compared with (78.53±47.63) U/ml in controls. The difference in serum level of EBV VCA IgG between both groups was statistically highly significant (P = &lt; 0.001). Conclusion There were higher levels of EBV VCA IgG in the serum of MS patients compared to healthy controls. This finding postulates a relation between EBV infection and MS and its role in the pathogenesis of MS.

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