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Journal of Virology, December 2005, p. 14956-14961, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14956-14961.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of E2 Binding to Brd4 Enhances Viral Genome Loss and Phenotypic Reversion of Bovine Papillomavirus-Transformed Cells

Jianxin You, Michal-Ruth Schweiger, and Peter M. Howley*

Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115

Received 12 June 2005/ Accepted 1 September 2005

The bovine papillomavirus E2 protein tethers the viral genomes to mitotic chromosomes in dividing cells through binding to the C-terminal domain (CTD) of Brd4. Expression of the Brd4-CTD competes the binding of E2 to endogenous Brd4 in cells. Here we extend our previous study that identified Brd4 as the E2 mitotic chromosome receptor to show that Brd4-CTD expression released the viral DNA from mitotic chromosomes in BPV-1 transformed cells. Furthermore, stable expression of Brd4-CTD enhanced the frequency of morphological reversion of BPV-1 transformed C127 cells resulting in the complete elimination of the viral DNA in the resulting flat revertants.

* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: (617) 432-2884. Fax: (617) 432-2882. E-mail: peter_howley{at}hms.harvard.edu.

Journal of Virology, December 2005, p. 14956-14961, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14956-14961.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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