Evolution of BK Virus Based on Complete Genome Data

Abstract

The human polyomavirus BK virus (BKV) is ubiquitous in humans, infecting children asymptomatically. BKV is the only primate polyomavirus that has subtypes (I-IV) distinguishable by immunological reactivity. Nucleotide (nt) variations in a major capsid protein (VP1) gene region (designated the epitope region), probably responsible for antigenic diversity, have been used to classify BKV isolates into subtypes. Here, with all the protein-encoding gene sequences, we attempted to elucidate the evolutionary relationships among 28 BKV isolates belonging to subtypes I, III, and IV (no isolate belonging to subtype II, a minor one, was included). First, using the GTR + Gamma + I model, maximum likelihood trees were reconstructed for individual viral genes as well as for concatenated viral genes. On the resultant trees, the 28 BKV isolates were consistently divided into three clades corresponding to subtypes I, III, and IV, although bootstrap probabilities are not always high. Then we used more sophisticated likelihood models, one of which takes account of codon structure, to elucidate the phylogenetic relationships among BKV subtypes, but the phylogeny of the deep branchings remained ambiguous. Furthermore, the possibility of positive selection in the evolution of BKV was examined using the nonsynonymous/synonymous rate ratio as a measure of selection. An analysis based on entire genes could not detect any strong evidence for positive selection, but that based on the epitope region identified a few sites potentially under positive selection (these sites were among those showing subtype linked polymorphisms).

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

“…Our findings raise the interesting question of whether different BKV genotypes or subgenotypes exhibit altered tissue tropism or different levels of virulence in vivo. Although previous studies have surveyed BKV genotypes found in nephropathic lesions (15,16,(37)(38)(39), these studies have relied on BKV-I-biased PCR primers that underestimate the abundance of BKV genotypes II, III, and IV (40). The possibility that commonly used PCR primers do not robustly detect non-genotype I BKVs (particularly in the case of individuals coinfected with multiple BKV genotypes) is consistent with our observation that BKV-II seroprevalence (Fig.…”

“…Based on initial phylogenetic analyses, we chose BKV representatives from each of the major branches of the tree, specifically BKV-Ia (isolate name BK-D; accession number JF894228), BKV-Ib1 (KOM-5; AB211374) (15), BKV-Ib2 (PittVR2; DQ989796) (16), BKV-Ic (RYU-2; AB211377) (15), BKV-II (GBR-12; AB263920) (17), BKV-III (KOM-3; AB211386) (15), BKV-IVb1 (THK-8; AB211390) (15), and BKV-IVc2 (A-66H; AB369093) (2,9). A codonmodified version of the VP1 gene of each variant was designed according to a previously reported algorithm (18), with the exception of variant KOM-5, which was expressed from an unmodified late region fragment that includes the native agnoprotein and VP2/3 genes (19).…”

Multiplex Real-Time PCR Assay for Simultaneous Quantification of BK Polyomavirus, JC Polyomavirus, and Adenovirus DNA

“…The sequences of the primer-probe sets used in this assay are nearly identical to those of BKPyV and JCPyV from Japan (16,23). The most commonly used strains outside Japan are Dunlop for BKPyV and Mad1 for JCPyV.…”

Occurrence of the European Subgroup of Subtype I BK Polyomavirus in Japanese-Americans Suggests Transmission outside the Family

“…2). The geographic origins of reference isolates were the United States (DUN), Kenya (KEN-1), South Africa (WW), Ethiopia (ETH-3), The Netherlands (Dik and JL), Finland (FNL-12), the United Kingdom (AS and GBR-12), and Japan (KOM-2, KOM-3, MT, RYU-2, RYU-3, THK-8, TW-1, and TW-3) (13,16,20,25 (Fig. 1).…”