Program in Bioinformatics and Integrative Biology; Division of Infectious Diseases and Immunology, Department of Medicine
Genetics and Genomics | Hemic and Lymphatic Diseases | Immune System Diseases | Immunology of Infectious Disease | Neoplasms | Pediatrics | Population Biology | Virology | Viruses
Endemic 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.
Epstein Barr virus, malaria, genome sequencing, genetic variation, endemic Burkitt Lymphoma, EBV type 1, EBV type 2, genomics
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 689216; doi: https://doi.org/10.1101/689216. Link to preprint on bioRxiv service.
Now published in Journal of Virology, 10.1128/JVI.02007-19
Kaymaz Y, Oduor C, Aydemir O, Luftig M, Otieno J, Ong'echa JM, Bailey JA, Moormann AM. (2019). Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/689216. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1692
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Genetics and Genomics Commons, Hemic and Lymphatic Diseases Commons, Immune System Diseases Commons, Immunology of Infectious Disease Commons, Neoplasms Commons, Pediatrics Commons, Population Biology Commons, Virology Commons, Viruses Commons