{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:36:18Z","timestamp":1780576578798,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK125418 to J. T. B. and B. L. L."],"award-info":[{"award-number":["R01 DK125418 to J. T. B. and B. L. L."]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>BK polyomavirus (BKPyV) infection is common after hematopoietic stem cell transplantation (HSCT) and is associated with the development of hemorrhagic cystitis (HC). The role that BKPyV plays in the pathogenesis of HC is not well characterized. We investigated the impact of BKPyV diversity on the development of HC using a previously established cohort of pediatric HSCT patients. There were 147 urine samples with quantifiable BKPyV at month 1 after HSCT; 137 (93.2%) were amplified using our in-house polymerase chain reaction approach and sent for next-generation sequencing. Subtype Ia was most frequent (61.3%), followed by subtype Ib1 (31.4%). The median viral load of subtype Ia samples was higher than for subtype Ib1 at month 1. Across the protein coding regions, APOBEC-induced mutations and signature patterns associated with HC were identified. This is the largest sequencing study of a single cohort of HSCT patients, providing a vast resource of sequence data for future analyses.<\/jats:p>","DOI":"10.1093\/infdis\/jiad117","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T11:36:25Z","timestamp":1682508985000},"page":"1208-1218","source":"Crossref","is-referenced-by-count":10,"title":["BK Polyomavirus Diversity After Hematopoietic Stem Cell Transplantation"],"prefix":"10.1093","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-9747","authenticated-orcid":false,"given":"Elizabeth A","family":"Odegard","sequence":"first","affiliation":[{"name":"Division of Digestive Diseases, University of Cincinnati College of Medicine , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi L","family":"Meeds","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, University of Cincinnati College of Medicine , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B","family":"Kleiboeker","sequence":"additional","affiliation":[{"name":"Eurofins Viracor Laboratories , Lenexa, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assem","family":"Ziady","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Ohio"},{"name":"Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Sabulski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Ohio"},{"name":"Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonata","family":"Jodele","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Ohio"},{"name":"Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix E","family":"Seif","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania , Pennsylvania"},{"name":"Division of Oncology, The Children's Hospital of Philadelphia , Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella M","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Ohio"},{"name":"Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L","family":"Laskin","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania , Pennsylvania"},{"name":"Division of Nephrology, The Children's Hospital of Philadelphia , Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2876-3811","authenticated-orcid":false,"given":"Jason T","family":"Blackard","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases, University of Cincinnati College of Medicine , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"2023110719203748600_jiad117-B1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000363","article-title":"Seroepidemiology of human polyomaviruses","volume":"5","author":"Kean","year":"2009","journal-title":"PLoS Pathog"},{"key":"2023110719203748600_jiad117-B2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1128\/CMR.00074-16","article-title":"BK polyomavirus: clinical aspects, immune regulation, and emerging therapies","volume":"30","author":"Ambalathingal","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"2023110719203748600_jiad117-B3","first-page":"12","article-title":"ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus\u2013associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients","volume":"73","author":"Cesaro","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2023110719203748600_jiad117-B4","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/bmt.2013.235","article-title":"High burden of BK virus\u2013associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation","volume":"49","author":"Gilis","year":"2014","journal-title":"Bone Marrow Transplant"},{"key":"2023110719203748600_jiad117-B5","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.bbmt.2009.12.009","article-title":"Late-onset hemorrhagic cystitis in children after hematopoietic stem cell transplantation for thalassemia and sickle cell Anemia: a prospective evaluation of polyoma (BK) virus infection and treatment with cidofovir","volume":"16","author":"Gaziev","year":"2010","journal-title":"Biol Blood Marrow Transplant"},{"key":"2023110719203748600_jiad117-B6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/jpids\/piu043","article-title":"A prospective study on the predictive value of plasma BK virus-DNA load for hemorrhagic cystitis in pediatric patients after stem cell transplantation","volume":"4","author":"Cesaro","year":"2014","journal-title":"J Pediatric Infect Dis Soc"},{"key":"2023110719203748600_jiad117-B7","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.bbmt.2011.02.012","article-title":"Blood, and not urine, BK viral load predicts renal outcome in children with hemorrhagic cystitis following hematopoietic stem cell transplantation","volume":"17","author":"Haines","year":"2011","journal-title":"Biol Blood Marrow Transplant"},{"key":"2023110719203748600_jiad117-B8","first-page":"1","article-title":"The natural history of BK polyomavirus and the host immune response after stem cell transplantation","volume":"32","author":"Laskin","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2023110719203748600_jiad117-B9","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1182\/bloodadvances.2019000802","article-title":"Presentation of BK polyomavirus-associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation","volume":"4","author":"Imlay","year":"2020","journal-title":"Blood Adv"},{"key":"2023110719203748600_jiad117-B10","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.micinf.2006.11.008","article-title":"Relationships between BK virus lineages and human populations","volume":"9","author":"Zheng","year":"2007","journal-title":"Microbes Infect"},{"key":"2023110719203748600_jiad117-B11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/rmv.613","article-title":"Evolution of the BK polyomavirus: epidemiological, anthropological and clinical implications","volume":"19","author":"Yogo","year":"2009","journal-title":"Rev Med Virol"},{"key":"2023110719203748600_jiad117-B12","doi-asserted-by":"crossref","DOI":"10.1002\/rmv.2102","article-title":"BK polyomavirus diversity\u2014why viral variation matters","volume":"30","author":"Blackard","year":"2020","journal-title":"Rev Med Virol"},{"key":"2023110719203748600_jiad117-B13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/jmv.1890280212","article-title":"Serological typing scheme for BK-like isolates of human polyomavirus","volume":"28","author":"Knowles","year":"1989","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B14","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/jmv.1890390110","article-title":"BK virus antigenic variants: sequence analysis within the capsid VP1 epitope","volume":"39","author":"Li","year":"1993","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B15","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.virusres.2010.01.017","article-title":"Polymorphisms of the BK virus subtypes and their influence on viral in vitro growth efficiency","volume":"149","author":"Tremolada","year":"2010","journal-title":"Virus Res"},{"key":"2023110719203748600_jiad117-B16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.virusres.2017.10.018","article-title":"BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients","volume":"243","author":"Varella","year":"2018","journal-title":"Virus Res"},{"key":"2023110719203748600_jiad117-B17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jcv.2019.02.002","article-title":"The detection of BKPyV genotypes II and IV after renal transplantation as a simple tool for risk assessment for PyVAN and transplant outcome already at early stages of BKPyV reactivation","volume":"113","author":"Korth","year":"2019","journal-title":"J Clin Virol"},{"key":"2023110719203748600_jiad117-B18","doi-asserted-by":"crossref","DOI":"10.1016\/j.jviromet.2021.114319","article-title":"Optimized amplification of BK polyomavirus in urine","volume":"299","author":"Odegard","year":"2022","journal-title":"J Virol Methods"},{"key":"2023110719203748600_jiad117-B19","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1099\/vir.0.79920-0","article-title":"Analysis of 15 novel full-length BK virus sequences from three individuals: evidence of a high intra-strain genetic diversity","volume":"85","author":"Chen","year":"2004","journal-title":"J Gen Virol"},{"key":"2023110719203748600_jiad117-B20","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1128\/JCM.01385-15","article-title":"Limited variation in BK virus T-cell epitopes revealed by next-generation sequencing","volume":"53","author":"Sahoo","year":"2015","journal-title":"J Clin Microbiol"},{"key":"2023110719203748600_jiad117-B21","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/bioinformatics\/bts091","article-title":"Unipro UGENE: a unified bioinformatics toolkit","volume":"28","author":"Okonechnikov","year":"2012","journal-title":"Bioinformatics"},{"key":"2023110719203748600_jiad117-B22","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"2023110719203748600_jiad117-B23","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol Biol Evol"},{"key":"2023110719203748600_jiad117-B24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ve\/vey016","article-title":"Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10","volume":"4","author":"Suchard","year":"2018","journal-title":"Virus Evol"},{"key":"2023110719203748600_jiad117-B25","first-page":"400","article-title":"Detecting hypermutations in viral sequences with an emphasis on G \u2192 A hypermutation","volume-title":"Bioinformatics","author":"Rose","year":"2000"},{"key":"2023110719203748600_jiad117-B26","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1089\/aid.1992.8.1549","article-title":"Signature pattern analysis: a method for assessing viral sequence relatedness","volume":"8","author":"Korber","year":"1992","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2023110719203748600_jiad117-B27","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1099\/vir.0.83611-0","article-title":"Distribution patterns of BK polyomavirus (BKV) subtypes and subgroups in American, European and Asian populations suggest co-migration of BKV and the human race","volume":"90","author":"Zhong","year":"2009","journal-title":"J Gen Virol"},{"key":"2023110719203748600_jiad117-B28","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/jmv.22147","article-title":"VP-1 quasispecies in human infection with polyomavirus BK","volume":"84","author":"Luo","year":"2012","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B29","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3390\/v13071366","article-title":"Human apobec3 variations and viral infection","volume":"13","author":"Sadeghpour","year":"2021","journal-title":"Viruses"},{"key":"2023110719203748600_jiad117-B30","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1128\/JVI.00771-16","article-title":"Functional upregulation of the DNA cytosine deaminase APOBEC3B by polyomaviruses","volume":"90","author":"Verhalen","year":"2016","journal-title":"J Virol"},{"key":"2023110719203748600_jiad117-B31","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.chom.2018.04.005","article-title":"Characterization of BK polyomaviruses from kidney transplant recipients suggests a role for APOBEC3 in driving in-host virus evolution","volume":"23","author":"Peretti","year":"2018","journal-title":"Cell Host Microbe"},{"key":"2023110719203748600_jiad117-B32","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00250-21","article-title":"In vivo generation of BK and JC polyomavirus defective viral genomes in human urine samples associated with higher viral loads","volume":"95","author":"Addetia","year":"2021","journal-title":"J Virol"},{"key":"2023110719203748600_jiad117-B33","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.20072097","article-title":"Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology","volume":"205","author":"Gosert","year":"2008","journal-title":"J Exp Med"},{"key":"2023110719203748600_jiad117-B34","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1002\/jmv.21605","article-title":"Functional analysis of polyomavirus BK non-coding control region quasispecies from kidney transplant recipients","volume":"81","author":"Olsen","year":"2009","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/tid.13269","article-title":"BK polyomavirus nephropathy with systemic viral spread: whole genome sequencing data from a fatal case of BKPyV infection","volume":"22","author":"Roy","year":"2020","journal-title":"Transpl Infect Dis"},{"key":"2023110719203748600_jiad117-B36","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/039463200501800213","article-title":"BKV infection and hemorrhagic cystitis after allogeneic bone marrow transplant","volume":"18","author":"Fioriti","year":"2005","journal-title":"Int J Immunopathol Pharmacol"},{"key":"2023110719203748600_jiad117-B37","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/jmv.20566","article-title":"Unique BK virus non-coding control region (NCCR) variants in hematopoietic stem cell transplant recipients with and without hemorrhagic cystitis","volume":"78","author":"Carr","year":"2006","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B38","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/jmv.20909","article-title":"Polyomavirus BK non-coding control region rearrangements in health and disease","volume":"79","author":"Sharma","year":"2007","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B39","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/jmv.23240","article-title":"Phylogenetic analysis of the complete genome of 11 BKV isolates obtained from allogenic stem cell transplant recipients in Ireland","volume":"84","author":"Drew","year":"2012","journal-title":"J Med Virol"},{"key":"2023110719203748600_jiad117-B40","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1128\/JVI.03625-14","article-title":"Sp1 sites in the noncoding control region of BK polyomavirus are key regulators of bidirectional viral early and late gene expression","volume":"89","author":"Bethge","year":"2015","journal-title":"J Virol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiad117\/50273993\/jiad117.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/228\/9\/1208\/52789714\/jiad117.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/228\/9\/1208\/52789714\/jiad117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T19:38:14Z","timestamp":1699385894000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/228\/9\/1208\/7143026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,4,26]]},"published-print":{"date-parts":[[2023,11,2]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiad117","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11,1]]},"published":{"date-parts":[[2023,4,26]]}}}