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Journal of Virology, January 2009, p. 640-650, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01936-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Human Papillomavirus Type 8 E2 Tethering Protein Targets the Ribosomal DNA Loci of Host Mitotic Chromosomes{triangledown}

Atasi Poddar, Shawna C. Reed, Maria G. McPhillips, Jonathan E. Spindler, and Alison A. McBride*

Laboratory of Viral Diseases, NIAID, NIH, Bethesda, Maryland

Received 15 September 2008/ Accepted 4 November 2008

For many papillomaviruses, the viral protein E2 tethers the viral genome to the host mitotic chromosomes to ensure persistent, long-term maintenance of the genome during cell division. Our previous studies of E2 proteins from different genera of papillomaviruses have shown that they bind to different regions of the host chromosomes during mitosis. For example, bovine papillomavirus type 1 (BPV-1) E2 binds to all chromosomes as small speckles in complex with the cellular protein Brd4. In contrast, the human papillomavirus type 8 (HPV-8) E2 protein binds as large speckles at the pericentromeric regions of chromosomes. Here we show that these speckles do not contain Brd4, and unlike that of BPV-1, the N-terminal Brd4-interacting domain of HPV-8 E2 is not required for chromosome binding. In contrast to BPV-1 E2, the HPV-8 E2 protein targets the short arms of acrocentric mitotic chromosomes. Furthermore, the E2 protein interacts with the repeated ribosomal DNA genes found in this location and colocalizes with UBF, the RNA polymerase I transcription factor. Therefore, HPV-8 E2 genome tethering occurs by a Brd4-independent mechanism through a novel interaction with specific regions of mitotic chromosomes. Thus, a wide range of viruses have adopted the strategy of linking their genomes to host chromosomes, but individual viruses use different chromosomal targets. Characterization of these targets will enable the development of antiviral therapies to eliminate the viral genomes from infected cells.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, NIAID, NIH, 4 Center Dr. MSC 0445, Bethesda, MD 20892. Phone: (301) 496-1370. Fax: (301) 480-1497. E-mail: amcbride{at}nih.gov

{triangledown} Published ahead of print on 12 November 2008.

Journal of Virology, January 2009, p. 640-650, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01936-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zheng, G., Schweiger, M.-R., Martinez-Noel, G., Zheng, L., Smith, J. A., Harper, J. W., Howley, P. M. (2009). Brd4 Regulation of Papillomavirus Protein E2 Stability. J. Virol. 83: 8683-8692 [Abstract] [Full Text]  
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