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Journal of Virology, May 2001, p. 4139-4149, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4139-4149.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The E8 Domain Confers a Novel Long-Distance Transcriptional Repression Activity on the E8^E2C Protein of High-Risk Human Papillomavirus Type 31

Frank Stubenrauch,* Thomas Zobel, and Thomas Iftner

Sektion Experimentelle Virologie, Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universitätsklinikum Tübingen, D-72076 Tübingen, Germany

Received 23 October 2000/Accepted 8 February 2001

Infections with high-risk human papillomaviruses (HPVs) are the major risk factor for the development of anogenital cancers. Viral E2 proteins are involved in viral DNA replication and regulation of transcription. Repression of the viral P97 promoter by E2 proteins has been implicated in the modulation of the immortalization capacity and DNA replication properties of high-risk HPVs. Analysis of the cis and trans requirements for repression of the HPV type 31 (HPV31) P97 promoter, however, revealed striking differences between the full-length E2 and the E8^E2C fusion protein which were due to conserved residues W6 and K7 of the E8 domain. In contrast to E2, E8^E2C completely inhibited the P97 promoter from a single promoter-distal E2 binding site. This novel long-distance repression activity of the E8 domain also enabled E8^E2C to inhibit the HPV6a P2 promoter and minimal-promoter constructs containing E2 binding sites. Thus, E8^E2C may represent the master repressor of viral gene expression during a high-risk HPV infection, and changes in the activity of E8^E2C might contribute to the progression of high-risk HPV-induced lesions.

* Corresponding author. Mailing address: Sektion Experimentelle Virologie, Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universitätsklinikum Tübingen, Calwerstr. 7/6, D-72076 Tübingen, Germany. Phone: 49-7071-2980247. Fax: 49-7071-295790. E-mail: frank.stubenrauch{at}med.uni-tuebingen.de.

Journal of Virology, May 2001, p. 4139-4149, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4139-4149.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lace, M. J., Anson, J. R., Thomas, G. S., Turek, L. P., Haugen, T. H. (2008). The E8{wedge}E2 Gene Product of Human Papillomavirus Type 16 Represses Early Transcription and Replication but Is Dispensable for Viral Plasmid Persistence in Keratinocytes. J. Virol. 82: 10841-10853 [Abstract] [Full Text]  
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