Chromosomal aberrations induced by BK virus T antigen in human fibroblasts

Human fibroblasts, transfected with a recombinant DNA containing the neo gene and BK virus (BKV) early region, which expresses BPV large T antigen (TAg), show cytogenetic alterations characterized by dicentric chromosomes and other structural aberrations such as deletions, duplications, translocations, and ring chromosomes. Such alterations were absent or significantly less frequent in human fibroblasts transfected with a plasmid expressing only the neo gene. The chromosome damage in BKV-transfected cells was evident before the appearance of the morphologically transformed phenotype and therefore seems to be a primary effect of TAg expression in human cells. The specific pattern of chromosome aberrations suggests the prevalence of an indirect clastogenic effect, determined by the inhibition of p53 regulatory functions on genome stability by BKV TAg. Due to the widespread distribution of BKV in the human population and to the latent state of BKV DNA in many human organs, the clastogenic activity of BKV TAg may potentially participate in an oncogenic process involving BKV latently infected cells.