PREVALENCE OF THE ARCHETYPAL REGULATORY REGION AND SEQUENCE POLYMORPHISMS IN NONPASSAGED BK VIRUS VARIANTS

Since the first isolation and characterization of BK virus (BKV), a number of BKV variants which differ in genomic structure or antigenic determinants have been described. The regulatory region, in particular, the enhancer elements, show the most divergent sequences among different isolates. The structural organization of a putative ancestral prototype or archetype, from which all of the variants are probably derived, has been proposed. By sequencing the regulatory regions of 13 different isolates from the urine of bone marrow transplant recipients, we determined the structures and sequences of BKV variants diffused in the human population. The enhancer region was amplified by polymerase chain reaction to avoid passage in culture, and the product was directly sequenced. The structure most frequently observed is in agreement with the postulated archetype, containing a single enhancer element with no repeats. By sequence analysis we identified four hot spots of nucleotide variation. These variations are consistent with the existence of two consensus sequences. One sequence motif, observed in about 85% of the isolates, is referred to as the archetypal BKV, while a second motif, observed in the remaining 15% of the variants, is highly reminiscent of the AS strain.