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Journal of Virology, May 2006, p. 4792-4800, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4792-4800.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Dynamic Localization of the Human Papillomavirus Type 11 Origin Binding Protein E2 through Mitosis While in Association with the Spindle Apparatus

Luan D. Dao,¹ Aaron Duffy,¹ Brian A. Van Tine,^2, Shwu-Yuan Wu,³ Cheng-Ming Chiang,³ Thomas R. Broker,¹ and Louise T. Chow^1*

Departments of Biochemistry and Molecular Genetics,¹ Pathology, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, Alabama 35294-0005,² Department of Biochemistry, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106-4935³

Received 15 October 2005/ Accepted 20 February 2006

Papillomaviral DNA replicates as extrachromosomal plasmids in squamous epithelium. Viral DNA must segregate equitably into daughter cells to persist in dividing basal/parabasal cells. We have previously reported that the viral origin binding protein E2 of human papillomavirus types 11 (HPV-11), 16, and 18 colocalized with the mitotic spindles. In this study, we show the localization of the HPV-11 E2 protein to be dynamic. It colocalized with the mitotic spindles during prophase and metaphase. At anaphase, it began to migrate to the central spindle microtubules, where it remained through telophase and cytokinesis. It was additionally observed in the midbody at cytokinesis. A peptide spanning residues 285 to 308 in the carboxyl-terminal domain of HPV-11 E2 (E2C) is necessary and sufficient to confer localization on the mitotic spindles. This region is conserved in HPV-11, -16, and -18 and bovine papillomavirus type 4 (BPV-4) E2 and is also required for the respective E2C to colocalize with the mitotic spindles. The E2 protein of bovine papillomavirus type 1 is tethered to the mitotic chromosomes via the cellular protein Brd4. However, the HPV-11 E2 protein did not associate with Brd4 during mitosis. Lastly, a chimeric BPV-1 E2C containing the spindle localization domain from HPV-11 E2C gained the ability to localize to the mitotic spindles, whereas the reciprocal chimera lost the ability. We conclude that this region of HPV E2C is critical for localization with the mitotic apparatus, enabling the HPV DNA to sustain persistent infections.

Present address: Department of Internal Medicine, 660 S. Euclid Ave., P.O. Box 8121, Washington University in St. Louis, St. Louis, MO 63110.

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