Polymorphisms of the four BKV subtypes and their influence on viral in vitro growth efficiency : a comparative study

SUMMARY Four different genomic subtypes of the ubiquitous human polyomavirus BKV have been identified. The existence of the BKV genomic subtypes is due to nucleotide polymorphisms clustered within the nucleotide sequence 1744-1812 of the major capsid protein VP1. These polymorphisms cause amino acid substitutions within the VP1 61-83 amino acidic region, which corresponds to the BC loop of SV40 and may play an important role in virus binding and entry to its host cell. To determine whether the polymorphisms of this VP1 region may affect the in vitro growth ability of the virus, we created recombinant viral genomes harboring the polymorphisms characteristic of the four viral subtypes within the same genomic background. We then performed in vitro infections and compared the growth efficiency of the four viral strains at different time points during the infection course. The results of our study indicated that the viral strains containing the nucleotide polymorphisms of subtypes I and II exhibited the highest replication ability in Vero cells and the same replication pattern. Subtype IV exhibited a lower growth efficiency, while the replication ability of subtype III was markedly reduced compare to that of the other subtypes. The results of our study showed that, as well as for the other polyomaviruses, the BC loop of BKV plays a crucial role in the virus lifecycle, as suggested by the fact that amino acid substitutions clustered within the VP1 61-83 region may profoundly affect the in vitro growth efficiency of the virus. The identification of amino acid residues that are critical for virus growth and viability might be useful to support, in the future, the development of new clinical tools for the treatment of BKV- associated diseases.