Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated

ABSTRACT BK polyomavirus (BKPyV) is a non-enveloped, double-stranded, circular DNA virus that is a member of the Polyomaviridae family. The BKPyV genome is divided into three regions, including the non-coding control region (NCCR), the early region, and the late region. BKPyV has one of the highest...

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Main Authors: Tiana A. Walder, Elizabeth A. Odegard, Heidi L. Meeds, Steven B. Kleiboeker, Assem Ziady, Anthony Sabulski, Sonata Jodele, Alix E. Seif, Stella M. Davies, Benjamin L. Laskin, Jason T. Blackard
Format: Article
Language:English
Published: American Society for Microbiology 2025-08-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.00494-25
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author Tiana A. Walder
Elizabeth A. Odegard
Heidi L. Meeds
Steven B. Kleiboeker
Assem Ziady
Anthony Sabulski
Sonata Jodele
Alix E. Seif
Stella M. Davies
Benjamin L. Laskin
Jason T. Blackard
author_facet Tiana A. Walder
Elizabeth A. Odegard
Heidi L. Meeds
Steven B. Kleiboeker
Assem Ziady
Anthony Sabulski
Sonata Jodele
Alix E. Seif
Stella M. Davies
Benjamin L. Laskin
Jason T. Blackard
author_sort Tiana A. Walder
collection DOAJ
description ABSTRACT BK polyomavirus (BKPyV) is a non-enveloped, double-stranded, circular DNA virus that is a member of the Polyomaviridae family. The BKPyV genome is divided into three regions, including the non-coding control region (NCCR), the early region, and the late region. BKPyV has one of the highest mutation rates among DNA viruses, and four genotypes have been identified based on amino acid variation within the VP1 region. Mutations within the NCCR have been noted, and this region exhibits hypervariability. Here, we show that many of the point mutations observed within the NCCR are genotype-associated, termed genotype-associated polymorphisms (GAPs). These GAPs correlate with regions of hypervariability, are inherent to their genotype, and can be used to genotype clinical strains, separate from other genomic regions. We also show that these GAPs fall within predicted transcription factor binding sites and therefore provide targets for further functional studies.IMPORTANCEBK Polyomavirus (BKPyV) is the cause of hemorrhagic cystitis in hematopoietic cell transplant recipients and BKPyV-associated nephropathy in renal transplant recipients and thus is an important determinant of transplant outcome. The viral mechanisms leading to disease manifestation remain to be thoroughly explored, but viral genetic variation has emerged as an area of interest. Understanding genomic diversity between and within BKPyV genotypes can provide sites of interest that may ultimately improve screening strategies and provide insights into the viral factors that contribute to disease.
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spelling doaj-art-b2ea726a1ca44251acfa235cab3a5dcc2025-08-20T04:00:44ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.00494-25Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associatedTiana A. Walder0Elizabeth A. Odegard1Heidi L. Meeds2Steven B. Kleiboeker3Assem Ziady4Anthony Sabulski5Sonata Jodele6Alix E. Seif7Stella M. Davies8Benjamin L. Laskin9Jason T. Blackard10Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USADivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USADivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAEurofins Viracor Laboratories, Lenexa, Kansas, USADepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USADepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USADepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USADepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USADivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USAABSTRACT BK polyomavirus (BKPyV) is a non-enveloped, double-stranded, circular DNA virus that is a member of the Polyomaviridae family. The BKPyV genome is divided into three regions, including the non-coding control region (NCCR), the early region, and the late region. BKPyV has one of the highest mutation rates among DNA viruses, and four genotypes have been identified based on amino acid variation within the VP1 region. Mutations within the NCCR have been noted, and this region exhibits hypervariability. Here, we show that many of the point mutations observed within the NCCR are genotype-associated, termed genotype-associated polymorphisms (GAPs). These GAPs correlate with regions of hypervariability, are inherent to their genotype, and can be used to genotype clinical strains, separate from other genomic regions. We also show that these GAPs fall within predicted transcription factor binding sites and therefore provide targets for further functional studies.IMPORTANCEBK Polyomavirus (BKPyV) is the cause of hemorrhagic cystitis in hematopoietic cell transplant recipients and BKPyV-associated nephropathy in renal transplant recipients and thus is an important determinant of transplant outcome. The viral mechanisms leading to disease manifestation remain to be thoroughly explored, but viral genetic variation has emerged as an area of interest. Understanding genomic diversity between and within BKPyV genotypes can provide sites of interest that may ultimately improve screening strategies and provide insights into the viral factors that contribute to disease.https://journals.asm.org/doi/10.1128/spectrum.00494-25BK polyomavirusnon-coding control regiongenotypesubtypesingle-nucleotide polymorphismsviral diversity
spellingShingle Tiana A. Walder
Elizabeth A. Odegard
Heidi L. Meeds
Steven B. Kleiboeker
Assem Ziady
Anthony Sabulski
Sonata Jodele
Alix E. Seif
Stella M. Davies
Benjamin L. Laskin
Jason T. Blackard
Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated
Microbiology Spectrum
BK polyomavirus
non-coding control region
genotype
subtype
single-nucleotide polymorphisms
viral diversity
title Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated
title_full Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated
title_fullStr Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated
title_full_unstemmed Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated
title_short Single-nucleotide polymorphisms within the BK polyomavirus non-coding control region are genotype-associated
title_sort single nucleotide polymorphisms within the bk polyomavirus non coding control region are genotype associated
topic BK polyomavirus
non-coding control region
genotype
subtype
single-nucleotide polymorphisms
viral diversity
url https://journals.asm.org/doi/10.1128/spectrum.00494-25
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