BK polyomavirus diversity-Why viral variation matters

Abstract

BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during childhood, and the majority of adults are latently infected. While BKV infection is rarely associated with clinical disease in most individuals, in immunosuppressed individuals, reactivation may cause kidney (BK-associated nephropathy) or bladder (hemorrhagic cystitis and ureteral stenosis) injury. No antiviral therapies have been approved for the treatment of BKV infection. Reducing immunosuppression is the most effective therapy, although this is not feasible in many patients. Thus, a robust understanding of viral pathogenesis and viral diversity remains important for the development of future therapeutic strategies. Studies of BKV diversity are quite sparse compared to other common viral infections; thus, much of our understanding of BVK variability and evolution relies heavily analogous studies of other viruses such as HIV or viral hepatitis. We provide a comprehensive review of BKV diversity at the population and individual level with careful consideration of how viral variability may impact viral replication, pathogenesis, tropism, and protein function. We also discuss a number of outstanding questions related to BK virus diversity that should be explored rigorously in future studies.

Keywords: BK polyomavirus; BK virus; diversity; evolution; variation.

FIGURE 1

Full-length BK genomes were downloaded from GenBank. For individuals with multiple sequences available, a single representative sequence was chosen for inclusion. 258 sequences were evaluated using a Bayesian inference approach as implemented in the BEAST v1.10.1 software and are labeled using their GenBank accession number and country of origin. Blue sequences belong to BK subtype I, green sequences to subtypes II/III, and red sequences to subtype IV

FIGURE 2

532 complete VP1 genes were downloaded from GenBank and aligned. Duplicate sequences were removed, and the resulting dataset is shown as a WebLogo with the height of each amino acid representing its relative proportion at that position of VP1

FIGURE 3

Full-length genomes from three studies of BK quasispecies diversity were downloaded from GenBank. Chen et al. studied one patient with HIV, one with Capillary Leak Syndrome, and one healthy control from the United States/West Africa. Takasaka et al. studied six renal transplant recipients from Japan. Kapusinszky et al. studied one pediatric renal transplant patient with nephropathy from the United States. Sequences were evaluated using a Bayesian inference approach labeled using their GenBank accession number and country of origin. Sequences are colored by their patient of origin