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We investigated the presence of different gene segments of HBV in plasma, B-cells and tumor tissues from DLBCL patients and explored the genetic variability of HBV within and across different compartments in a host using Next Generation Sequencing. Despite all 40 patients being HBV seronegative, 68% showed evidence of occult HBV. Sequencing of these gene segments revealed inter-compartment viral variants in 26% of them, each with at least one non-synonymous mutation. Between compartments, core gene variants revealed Arg94Leu, Glu86Arg and Ser41Thr while X gene variants revealed Phe73Val, Ala44Val, Ser146Ala and Ser147Pro. In tumor compartments <jats:italic>per se<\/jats:italic>, several mis-sense mutations were detected, notably the classic T1762A\/A1764G mutation in the basal core promoter. In addition, a virus surface antigen mis-sense mutation resulting in M125T was detected in all the samples and could account for surface antigen negativity and occult HBV status. It would be interesting to further explore if a temporal accumulation of viral variants within a favored niche, like patients\u2019 lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.<\/jats:p>","DOI":"10.1038\/s41598-019-51157-1","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T10:32:32Z","timestamp":1570703552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection"],"prefix":"10.1038","volume":"9","author":[{"given":"Mahua","family":"Sinha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keerthana","family":"Sundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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