{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:20:43Z","timestamp":1791822043033,"version":"4.3.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008375","name":"University of Basel","doi-asserted-by":"crossref","award":["MM2109"],"award-info":[{"award-number":["MM2109"]}],"id":[{"id":"10.13039\/100008375","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010455","name":"Swiss Transplant Cohort Study","doi-asserted-by":"crossref","award":["FUP148"],"award-info":[{"award-number":["FUP148"]}],"id":[{"id":"10.13039\/501100010455","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>High-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To identify molecular markers of BKPyV replication and disease, we scrutinized BKPyV DNA-loads in longitudinal urine and plasma pairs from 20 HCT patients using quantitative nucleic acid testing (QNAT), DNase-I treatment prior to QNAT, next-generation sequencing (NGS), and tested cell-mediated immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that larger QNAT amplicons led to under-quantification and false-negatives results (P &amp;lt; .001). DNase-I reduced urine and plasma BKPyV-loads by &amp;gt;90% (P &amp;lt; .001), indicating non-encapsidated BKPyV genomes. DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV genome fragmentation of \u2264250 bp impaired NGS coverage of genetic variation using 1000-bp and 5000-bp amplicons. Conversely, 250-bp amplicons captured viral minority variants. We identified genotype-specific and genotype-independent changes in capsid Vp1 or T-antigen predicted to escape from antibody neutralization or cytotoxic CD8 T-cells, respectively. Genotype-specific changes in immunodominant 9mers were associated with reduced or absent CD8 T-cell responses. Thus, failure to control BKPyV replication in HCT Patients may involve insufficient genotype-specific cytotoxic CD8 T-cell responses, potentially predictable by low neutralizing antibodies as well as genotype-independent immune escape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results provide new insights for patient evaluation and for designing immune protection through neutralizing antibodies, adoptive T-cell therapy, or vaccines.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiac450","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:32:24Z","timestamp":1668645144000},"page":"888-900","source":"Crossref","is-referenced-by-count":20,"title":["Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients"],"prefix":"10.1093","volume":"227","author":[{"given":"Karoline","family":"Leuzinger","sequence":"first","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"},{"name":"Clinical Virology, University Hospital Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Frank","sequence":"additional","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A","family":"Hillenbrand","sequence":"additional","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian H","family":"Weissbach","sequence":"additional","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0883-0423","authenticated-orcid":false,"given":"Hans H","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Transplantation and Clinical Virology, Department Biomedicine, University of Basel , Basel , Switzerland"},{"name":"Clinical Virology, University Hospital Basel , Basel , Switzerland"},{"name":"Infectious Diseases and Hospital Epidemiology, University Hospital Basel , Basel , 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