Abstract
Human BK polyomavirus (BKPyV) prevalence has been increasing due to the introduction of more potent immunosuppressive agents in transplant recipients, and its clinical interest. BKPyV has been linked mostly to polyomavirus-associated hemorrhagic cystitis, in allogenic hematopoietic stem cell transplant, and polyomavirus-associated nephropathy in kidney transplant patients. BKPyV is a circular double-stranded DNA virus that encodes for seven proteins, of which Viral Protein 1 (VP1), the major structural protein, has been extensively used for genotyping. BKPyV also contains the noncoding control region (NCCR), configured by five repeat blocks (OPQRS) known to be highly repetitive and diverse, and linked to viral infectivity and replication. BKPyV genetic diversity has been mainly studied based on the NCCR and VP1, due to the high occurrence of BKPyV-associated diseases in transplant patients and their clinical implications. Here BKTyper is presented, a free online genotyper for BKPyV, based on a VP1 genotyping and a novel algorithm for NCCR block identification. VP1 genotyping is based on a modified implementation of the BK typing and grouping regions (BKTGR) algorithm, providing a maximum-likelihood phylogenetic tree using a custom internal BKPyV database. Novel NCCR block identification relies on a minimum of 12-bp motif recognition and a novel sorting algorithm. A graphical representation of the OPQRS block organization is provided.
Highlights
Human BK polyomavirus (BKPyV), or Human polyomavirus 1, was first described in 1971 by Gardner and collaborators [1]
BKPyV has been mostly linked to two different transplantation diseases, polyomavirus-associated hemorrhagic cystitis (PyVHC) (5–15% of allogeneic hematopoietic stem cell transplant) [2] and polyomavirus-associated nephropathy (PyVAN) (1–10% of kidney transplant recipients) [3]
A maximum likelihood (ML) tree is computed at the BK typing and grouping regions (BKTGR) (BK typing and grouping region) using IQTree [27], with Mafft’s multiple-sequencing alignment (MSA)
Summary
Human BK polyomavirus (BKPyV), or Human polyomavirus 1, was first described in 1971 by Gardner and collaborators [1]. Morel et al designed a strategy to subtype BKPyV, based on a 100 bp amplicon, called the BK typing and grouping region (BKTGR) [13]. In this same study, Morel et al suggest a subtyping algorithm, validated through multiple sequence alignment and phylogeny. Rearrangements appear not to correlate with viral reactivation disease and development, but with early and late gene expression and overall viral replication, coincidently with the high prevalence of transcriptional factor binding motifs [4,18,19]. BKTyper can be found as an online free service (http://bktyper.zidu.be/) or on GitHub (https://github.com/joanmarticarreras/BKTyper) for local installation
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