Structural implications of BK polyomavirus sequence variations in the major viral capsid protein Vp1 and large T-antigen: a computational study Article Swipe
Janani Durairaj
,
Océane M. Follonier
,
Karoline Leuzinger
,
Leila T. Alexander
,
Maud Wilhelm
,
Joana Pereira
,
Caroline A. Hillenbrand
,
Fabian H. Weissbach
,
Torsten Schwede
,
Hans H. Hirsch
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.12.21.572635
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.12.21.572635
BK polyomavirus (BKPyV) is a double-stranded DNA virus causing nephropathy, hemorrhagic cystitis, and urothelial cancer in transplant patients. The BKPyV-encoded capsid protein Vp1 and large T-antigen (LTag) are key targets of neutralizing antibodies and cytotoxic T-cells, respectively. Our single-center data suggested that variability in Vp1 and LTag may contribute to failing BKPyV-specific immune control, and impact vaccine design. We therefore analyzed all available entries in GenBank (1516 VP1 ; 742 LTAG) and explored potential structural effects using computational approaches. BKPyV-genotype (gt)1 was found in 71.18% of entries, followed by BKPyV-gt4 (19.26%), BKPyV-gt2 (8.11%) and BKPyV-gt3 (1.45%), but rates differed according to country and specimen type. Vp1-mutations matched a serotype different than the assigned one or were serotype-independent in 43%, 18% affected more than one amino acid. Notable Vp1-mutations altered antibody-binding domains, interactions with sialic acid receptors, or were predicted to change conformation. LTag-sequences were more conserved, with only 16 mutations detectable in more than one entry and without significant effects on LTag-structure or interaction domains. However, LTag changes were predicted to affect HLA-class I presentation of immunodominant 9mers to cytotoxic T-cells. These global data strengthen single center observations and specifically our earlier findings revealing mutant 9mer epitopes conferring immune escape from HLA-I cytotoxic T cells. We conclude that variability of BKPyV-Vp1 and LTag may have important implications for diagnostic assays assessing BKPyV-specific immune control and for vaccine design. IMPORTANCE Type and rate of amino acid variations in BKPyV may provide important insights into BKPyV diversity in human populations and an important step towards defining determinants of BKPyV-specific immunity needed to protect vulnerable patients from BKPyV diseases. Our analysis of BKPyV sequences obtained from human specimens reveals an unexpectedly high genetic variability for this double-stranded DNA virus that strongly relies on host cell DNA replication machinery with its proof reading and error correction mechanisms. BKPyV variability and immune escape should be taken into account when designing further approaches to antivirals, monoclonal antibodies and vaccines for patients at risk of BKPyV diseases.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.12.21.572635
- https://www.biorxiv.org/content/biorxiv/early/2023/12/21/2023.12.21.572635.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390111028
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4390111028Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2023.12.21.572635Digital Object Identifier
- Title
-
Structural implications of BK polyomavirus sequence variations in the major viral capsid protein Vp1 and large T-antigen: a computational studyWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-12-21Full publication date if available
- Authors
-
Janani Durairaj, Océane M. Follonier, Karoline Leuzinger, Leila T. Alexander, Maud Wilhelm, Joana Pereira, Caroline A. Hillenbrand, Fabian H. Weissbach, Torsten Schwede, Hans H. HirschList of authors in order
- Landing page
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https://doi.org/10.1101/2023.12.21.572635Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/12/21/2023.12.21.572635.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2023/12/21/2023.12.21.572635.full.pdfDirect OA link when available
- Concepts
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Capsid, Epitope, Virology, Biology, Cytotoxic T cell, BK virus, Antigen, Antibody, Serotype, Human leukocyte antigen, Virus, Genetics, Kidney, Kidney transplantation, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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46Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| cited_by_percentile_year.min | 91 |
| corresponding_author_ids | https://openalex.org/A5020196535 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I1850255, https://openalex.org/I2802542264 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7400000095367432 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.72073633 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |