Genotyping schemes for polyomavirus BK, using gene-specific phylogenetic trees and single nucleotide polymorphism...

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• BK virus (BKV) genotyping traditionally relies on partial VP1 gene sequencing.
• This method's accuracy in distinguishing BKV subtypes and subgroups is questioned.
• Re-evaluation of current BKV genotyping practices is necessary.

Purpose of the Study:

• To reassess the reliability of historical BKV genotyping methods.
• To compare phylogenetic analyses using whole-genome, VP1, and large T-antigen (LTA) sequences.
• To identify single nucleotide polymorphisms (SNPs) for accurate BKV classification.

Main Methods:

• Phylogenetic tree construction using whole-genome and gene-specific sequences (VP1, LTA).
• Single nucleotide polymorphism (SNP) analysis of 162 publicly available BKV sequences.
• Comparative analysis of bootstrap values and classification congruence between different genomic regions.

Main Results:

• Partial VP1 gene sequencing is insufficient for reliable BKV subtype and subgroup determination.
• LTA-based phylogenetic trees provide superior resolution for subtype I subgroups (Ia, Ib1, Ib2, Ic) compared to VP1.
• Whole-genome analysis offers better resolution for subtype IV subgroups than LTA alone.
• A minimal set of four LTA SNPs can distinguish the four major BKV subtypes.
• VP1 gene lacks specific SNPs for subtypes II, IVa, and IVb, but shows genetic linkage with LTA.

Conclusions:

• Current BKV genotyping based solely on VP1 gene sequences is inadequate.
• Whole-genome and LTA phylogenetic analyses are more robust for accurate BKV classification.
• Specific LTA SNPs can be utilized for precise identification of major BKV subtypes.
• Despite limitations in VP1, VP1 and LTA regions exhibit genetic linkage, suggesting conserved evolutionary patterns.