Phylogenetic Analysis of Polyomavirus BK Sequences

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Abstract
Polyomavirus BK (BKV) has emerged as an important pathogen in kidney transplant patients. Existing taxonomic classifications of BKV come from conventional DNA sequence alignments based on limited data derived from the VP1 gene. We have used a phylogenetic whole-genome approach to examine the pattern of diversity and evolutionary relationships between 45 BKV strains isolated from multiple clinical settings. This analysis supports the classification of BKV into six genotypes, of which types V and VI have not been previously recognized. BKV strains hitherto classified as type I are, in fact, quite heterogeneous, and several cluster with our newly defined genotypes V and VI. The sequence information needed for assigning genotypes can be captured by VP1, VP2, VP3, or large T-gene sequencing. The most polymorphic coding region in the viral genome is VP1, but significant variation is also present in the large T-antigen gene, wherein polymorphisms are found in 11.39% of all nucleotide sites, 46.22% of which are cluster specific. Type-specific amino acid changes within the VP1 region are predicted to map to the BC and DE loops. The number of taxonomically informative amino acid changes in the large T antigen exceeds even that of the VP1 region. Viral strains isolated from healthy subjects and from patients with human immunodeficiency virus infection, Wiskott-Aldrich syndrome, and vasculopathy with capillary leak syndrome formed distinct subclusters. However, within the kidney transplant population, BKV strains derived from patients with asymptomatic viruria did not show complete separation from strains associated with allograft nephropathy.