Chimeric BK virus DNA episomes in a papillary urothelial bladder carcinoma

Abstract

BK virus (BKV) DNA sequences were identified in a papillary urothelial bladder carcinoma by Southern blot hybridization. The carcinoma contained both integrated and extrachromosomal DNA. Integrated sequences had a clonal restriction pattern, suggesting that BKV was integrated at some early stage of neoplastic initiation or progression. Viral episomes consisted of a population of covalent polymers based on a high-molecular-weight DNA unit, about 11-12 kb in size. DNA sequences non-homologous to the BKV genome were encompassed within DNA episomes, suggestive of acquisition of cellular sequences by viral DNA replication at the integration site. Extrachromosomal, chimeric DNA molecules were present at an average level of about 50 copies per cell, but their size, apparently incompatible with viral assembly, showed that BKV productive infection was impaired. The data suggest that infected cells underwent reversible changes affecting autonomous BKV DNA replication.