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Journal of Virology, May 1999, p. 4404-4412, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Long-Term Episomal Maintenance of Bovine Papillomavirus Type 1 Plasmids Is Determined by Attachment to Host Chromosomes, Which Is Mediated by the Viral E2 Protein and Its Binding Sites

Ivar Ilves,1 Sirje Kivi,2 and Mart Ustav1,*

Department of Microbiology and Virology1 and Department of Cell Biology,2 Institute of Molecular and Cell Biology, Estonian Biocentre, Tartu University, 51010 Tartu, Estonia

Received 21 October 1998/Accepted 19 January 1999

Papillomavirus genomes are stably maintained as extrachromosomal nuclear plasmids in dividing host cells. To address the mechanisms responsible for stable maintenance of virus, we examined nuclear compartmentalization of plasmids containing the full-length upstream regulatory region (URR) from the bovine papillomavirus type 1 (BPV1) genome. We found that these plasmids are tightly associated with the nuclear chromatin both in the stable cell lines that maintain episomal copies of the plasmids and in transiently transfected cells expressing the viral E1 and E2 proteins. Further analysis of viral factors revealed that the E2 protein in trans and its multiple binding sites in cis are both necessary and sufficient for the chromatin attachment of the plasmids. On the other hand, the BPV1 URR-dependent plasmid replication and chromatin attachment processes are clearly independent of each other. The ability of the plasmids to stably maintain episomes correlates clearly with their chromatin association function. These data suggest that viral E2 protein-mediated attachment of BPV1 genomes to the host cell chromatin could provide a mechanism for the coupling of viral genome multiplication and partitioning to the host cell cycle during viral latent infection.


* Corresponding author. Mailing address: Department of Microbiology and Virology, Institute of Molecular and Cell Biology, Tartu University, 23 Riia St., Tartu 51010, Estonia. Phone: 372-7-375047. Fax: 372-7-420286. E-mail: ustav{at}ebc.ee.


Journal of Virology, May 1999, p. 4404-4412, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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