Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection
Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). We investigated the presence of different gene segments of HBV in plasma, B-cells and tumor tissues from DLBCL patients and explored the genetic...
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creator | Sinha, Mahua Sundar, Keerthana Premalata, C. S. Asati, Vikas Murali, Alka Bajpai, Akhilesh Kumar Davuluri, Sravanthi Acharya, Kshitish K. Lakshmaiah, K. C. Babu K., Govind Jacob, Linu A. Nandan, Dharam Velayutham, Dinesh Datta, Sibnarayan Jayshree, R. S. |
description | Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). 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
per se
, 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’ lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL. |
doi_str_mv | 10.1038/s41598-019-51157-1 |
format | Article |
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per se
, 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’ lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-51157-1</identifier><identifier>PMID: 31601912</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/22 ; 45/23 ; 45/77 ; 692/4028/67/1858 ; 692/699/1541/1990/291/1621/1915 ; Adult ; Aged ; Aged, 80 and over ; Antigens ; B-cell lymphoma ; DNA, Viral - genetics ; Genetic variability ; Genetic Variation ; Hepatitis ; Hepatitis B ; Hepatitis B - complications ; Hepatitis B - virology ; Hepatitis B Surface Antigens - genetics ; Hepatitis B virus - classification ; High-Throughput Nucleotide Sequencing ; Humanities and Social Sciences ; Humans ; Immunohistochemistry ; Lymphocytes ; Lymphocytes B ; Lymphoma ; Lymphoma, Large B-Cell, Diffuse - virology ; Middle Aged ; multidisciplinary ; Mutation ; Mutation, Missense ; Next-generation sequencing ; Non-Hodgkin's lymphoma ; Prospective Studies ; Quasispecies ; Science ; Science (multidisciplinary) ; Young Adult</subject><ispartof>Scientific reports, 2019-10, Vol.9 (1), p.14516-8, Article 14516</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-9fe8b5680b5c94faa64e9a4177300e762b57be68abcb975a38381f5ece01a813</citedby><cites>FETCH-LOGICAL-c474t-9fe8b5680b5c94faa64e9a4177300e762b57be68abcb975a38381f5ece01a813</cites><orcidid>0000-0002-7872-8726 ; 0000-0001-6953-1510 ; 0000-0002-9425-7266</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787061/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787061/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31601912$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sinha, Mahua</creatorcontrib><creatorcontrib>Sundar, Keerthana</creatorcontrib><creatorcontrib>Premalata, C. S.</creatorcontrib><creatorcontrib>Asati, Vikas</creatorcontrib><creatorcontrib>Murali, Alka</creatorcontrib><creatorcontrib>Bajpai, Akhilesh Kumar</creatorcontrib><creatorcontrib>Davuluri, Sravanthi</creatorcontrib><creatorcontrib>Acharya, Kshitish K.</creatorcontrib><creatorcontrib>Lakshmaiah, K. C.</creatorcontrib><creatorcontrib>Babu K., Govind</creatorcontrib><creatorcontrib>Jacob, Linu A.</creatorcontrib><creatorcontrib>Nandan, Dharam</creatorcontrib><creatorcontrib>Velayutham, Dinesh</creatorcontrib><creatorcontrib>Datta, Sibnarayan</creatorcontrib><creatorcontrib>Jayshree, R. S.</creatorcontrib><title>Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). 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
per se
, 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’ lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.</description><subject>45</subject><subject>45/22</subject><subject>45/23</subject><subject>45/77</subject><subject>692/4028/67/1858</subject><subject>692/699/1541/1990/291/1621/1915</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens</subject><subject>B-cell lymphoma</subject><subject>DNA, Viral - genetics</subject><subject>Genetic variability</subject><subject>Genetic Variation</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B - complications</subject><subject>Hepatitis B - virology</subject><subject>Hepatitis B Surface Antigens - genetics</subject><subject>Hepatitis B virus - classification</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Lymphoma, Large B-Cell, Diffuse - virology</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Mutation, Missense</subject><subject>Next-generation sequencing</subject><subject>Non-Hodgkin's lymphoma</subject><subject>Prospective Studies</subject><subject>Quasispecies</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Young Adult</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1vFiEUhYnR2KbtH3BhSNy4cCwfw8BsTGz9aJMmumjcEgbvvC_NDEyBqenG3y70rbW6kA2E-9zDPRyEXlDylhKujlNLRa8aQvtGUCpkQ5-gfUZa0TDO2NNH5z10lNIVKUuwvqX9c7THaVcaKdtHP7_G0ARvwwa8s2-w8zkavA0p4xsXzYSvV5NcWsA6SKWKP7hxXBPgycQN4BNsYZrwdDsv2zAbvJjswOeEf7i8xcHadcr4DOp1dqng31xcq84INrvgD9Gz0UwJju73A3T56ePl6Vlz8eXz-en7i8a2ss1NP4IaRKfIIGzfjsZ0LfSmpVJyQkB2bBBygE6ZwQ69FIYrrugowAKhRlF-gN7tZJd1mOG7hepy0kt0s4m3Ohin_654t9WbcKM7qSTpqsDre4EYrldIWc8uVevGQ1iTZpwI0qryvwV99Q96Fdboi7tKccmElJViO8rGkFKE8WEYSnQNWO8C1iUnfRewrlO8fGzjoeV3nAXgOyCVkt9A_PP2f2R_AXHBsvI</recordid><startdate>20191010</startdate><enddate>20191010</enddate><creator>Sinha, Mahua</creator><creator>Sundar, Keerthana</creator><creator>Premalata, C. 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S. ; Asati, Vikas ; Murali, Alka ; Bajpai, Akhilesh Kumar ; Davuluri, Sravanthi ; Acharya, Kshitish K. ; Lakshmaiah, K. C. ; Babu K., Govind ; Jacob, Linu A. ; Nandan, Dharam ; Velayutham, Dinesh ; Datta, Sibnarayan ; Jayshree, R. 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S.</au><au>Asati, Vikas</au><au>Murali, Alka</au><au>Bajpai, Akhilesh Kumar</au><au>Davuluri, Sravanthi</au><au>Acharya, Kshitish K.</au><au>Lakshmaiah, K. C.</au><au>Babu K., Govind</au><au>Jacob, Linu A.</au><au>Nandan, Dharam</au><au>Velayutham, Dinesh</au><au>Datta, Sibnarayan</au><au>Jayshree, R. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-10-10</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>14516</spage><epage>8</epage><pages>14516-8</pages><artnum>14516</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). 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
per se
, 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’ lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31601912</pmid><doi>10.1038/s41598-019-51157-1</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7872-8726</orcidid><orcidid>https://orcid.org/0000-0001-6953-1510</orcidid><orcidid>https://orcid.org/0000-0002-9425-7266</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 45 45/22 45/23 45/77 692/4028/67/1858 692/699/1541/1990/291/1621/1915 Adult Aged Aged, 80 and over Antigens B-cell lymphoma DNA, Viral - genetics Genetic variability Genetic Variation Hepatitis Hepatitis B Hepatitis B - complications Hepatitis B - virology Hepatitis B Surface Antigens - genetics Hepatitis B virus - classification High-Throughput Nucleotide Sequencing Humanities and Social Sciences Humans Immunohistochemistry Lymphocytes Lymphocytes B Lymphoma Lymphoma, Large B-Cell, Diffuse - virology Middle Aged multidisciplinary Mutation Mutation, Missense Next-generation sequencing Non-Hodgkin's lymphoma Prospective Studies Quasispecies Science Science (multidisciplinary) Young Adult |
title | Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection |
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