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Folly Beach Library
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Edgar Allan Poe/Sullivan's Island Library
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Wando Mount Pleasant Library
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Village Library
9 a.m. – 6 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
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Otranto Road Library
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McClellanville Library
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Keith Summey North Charleston Library
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Hurd/St. Andrews Library
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Phone: (843) 805-6930
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Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation.
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- Author(s): Leuzinger, Karoline; Kaur, Amandeep; Wilhelm, Maud; Frank, Konstantin; Hillenbrand, Caroline A; Weissbach, Fabian H; Hirsch, Hans H
- Source:
Journal of Infectious Diseases; Apr2023, Vol. 227 Issue 7, p888-900, 13p- Subject Terms:
- Source:
- Additional Information
- Abstract:
Background: High-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis (BKPyV-HC).Methods: 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.Results: We found that larger QNAT amplicons led to under-quantification and false-negatives results (p < 0.001). DNase-I reduced urine and plasma BKPyV-loads by >90% (p < 0.001) indicating non-encapsidated BKPyV-genomes. DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV-genome fragmentation of ≤250 bp impaired NGS-coverage of genetic variation using 1000 bp and 5000 bp targets. Conversely, 250bp-amplicons captured viral minority variants. We identified genotype-specific and genotype-independent changes in capsid-Vp1 or large T-antigen predicted to escape from antibody neutralization or HLA-presentation to 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 of variants.Conclusion: Our results provide new insights for patient evaluation and for designing immune protection through neutralizing antibodies, adoptive T-cell therapy or vaccines. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of Journal of Infectious Diseases is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
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