Long-term episomal maintenance of bovine papillomavirus type 1 plasmids isdetermined by attachment to host chromosomes, which is mediated by the viral E2 protein and its binding sites

Papillomavirus genomes are stably maintained as extrachromosomal nuclear pl asmids in dividing host cells. To address the mechanisms responsible for st able maintenance of virus, we examined nuclear compartmentalization of plas mids containing the full-length upstream regulatory region (URR) from the b ovine papillomavirus type 1 (BPV1) genome. We found that these plasmids are tightly associated with the nuclear chromatin both in the stable cell line s that maintain episomal copies of the plasmids and in transiently transfec ted cells expressing the viral E1 and E2 proteins. Further analysis of vira l factors revealed that the E2 protein in trans and its multiple binding si tes in cis are both necessary and sufficient for the chromatin attachment o f the plasmids. On the other hand, the BPV1 URR-dependent plasmid replicati on and chromatin attachment processes are clearly independent of each other . The ability of the plasmids to stably maintain episomes correlates clearl y with their chromatin association function. These data suggest that viral E2 protein-mediated attachment of BPV1 genomes to the host cell chromatin c ould provide a mechanism for the coupling of viral genome multiplication an d partitioning to the host cell cycle during viral latent infection.