At least two types of control regions can be found among naturally occurring BK virus strains

The various strains of BK virus (BKV) exhibit a remarkable degree of heterogeneity in the transcriptional control region, which may affect the biological characteristics of a BKV strain. We describe the detection and sequencing of BKV control regions directly from urine samples and after propagation in cell culture. A BKV strain [BKV (TU)] with a control region anatomy not described earlier, as well as a BKV (WW)-like strain [BKV (WWT)], was detected in urine samples by direct sequencing of polymerase chain reaction products. Urine inocula containing BKV (WWT) yielded BKV (TU) upon one passage in cell culture, while BKV (TU) did not change its control region during propagation in cell culture. Analysis of the nucleotide sequence of the transcriptional control regions revealed a partial deletion and duplication in BKV (TU) compared with BKV (WWT). In addition, the control region of BKV (TU) contains two point mutations relative to BKV (WWT). This indicates that both virus strains were probably present in the BKV (WWT)-dominated urine inocula, rather than that BKV (WWT) genomes were rearranged into BKV (TU) genomes during cell propagation. The heterogeneity of the control region of BKV strains is discussed in relation to both confirmed and putative transcription factor-binding sites.