BK virus (BKV) genotyping has been historically based on nucleotides 1744 to 1812 in the VP1 gene. We reevaluated this practice by making BKV whole-genome and gene-specific phylogenetic trees as well as performing single nucleotide polymorphism (SNP) analysis of 162 sequences available in the public domain. It was found that currently known BKV subtypes and subgroups can no longer be reliably determined by sequencing certain partial gene sequences. Phylogenetic trees based on large T-antigen (LTA) allow separation of subtype I into subgroups Ia, Ib1, Ib2, and Ic, with bootstrap values of 100%, which are better than bootstraps obtained using VP1 sequences (bootstrap values of 71 to 97%). Subtype IV can be subdivided into subgroups, but LTA bootstrap values (33 to 80%) are lower than those obtained by whole-genome analysis (68 to 87%). Subtypes V and VI provisionally identified earlier on the basis of more limited sequence data are better classified as subgroups Ib2 and Ib1, respectively. LTA positions 3634, 3772, 3934, and 4339 can serve as a minimal SNP set to distinguish between the four major BKV subtypes. No subtype II-, IVa-, or IVb-defining SNPs are available in the VP1 gene. However, the overall congruence of viral strain classification based on either VP1 or LTA phylogenetic analysis indicates that these two areas of the viral genome are genetically linked. Interstrain genetic recombination between distant loci in the VP1 and LTA areas is not a common event.
