This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Park, R. B.
Right arrow Articles by Androphy, E. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, R. B.
Right arrow Articles by Androphy, E. J.

 Previous Article  |  Next Article 

Journal of Virology, November 2002, p. 11359-11364, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11359-11364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Genetic Analysis of High-Risk E6 in Episomal Maintenance of Human Papillomavirus Genomes in Primary Human Keratinocytes

Regina B. Park1,{dagger} and Elliot J. Androphy1,2*

Department of Molecular Biology and Microbiology, Tufts University School of Medicine,1 Department of Dermatology, Tufts-New England Medical Center, Boston, Massachusetts2

Received 21 May 2002/ Accepted 13 August 2002

Papillomaviruses possess small DNA genomes that encode five early (E) proteins. Transient DNA replication requires activities of the E1 and E2 proteins and a DNA segment containing their binding sites. The E6 and E7 proteins of cancer-associated human papillomavirus (HPV) transform cells in culture. Recent reports have shown that E6 and E7 are necessary for episomal maintenance of HPV in primary keratinocytes. The functions of E6 necessary for viral replication have not been determined, and to address this question we used a recently developed transfection system based on HPV31. To utilize a series of HPV16 E6 mutations, HPV31 E6 was replaced by its HPV16 counterpart. This chimeric genome was competent for both transient and stable replication in keratinocytes. Four HPV16 E6 mutations that do not stimulate p53 degradation were unable to support stable viral replication, suggesting this activity may be necessary for episomal maintenance. E7 has also been shown to be essential for episomal maintenance of the HPV31 genome. A point mutation in the Rb binding motif of HPV E7 has been reported to render HPV31 unable to stably replicate. Interestingly, HPV31 genomes harboring two of the three p53 degradation-defective E6 mutations combined with this E7 mutation were maintained as replicating episomes. These findings imply that the balance between E6 and E7 functions in infected cells is critical for episomal maintenance of high-risk HPV genomes. This model will be useful to dissect the activities of E6 and E7 necessary for viral DNA replication.

* Corresponding author. Present address: University of Massachusetts Medical School, LRB 328, 364 Plantation St., Worcester, MA 01605-2324. Phone: (508) 856-6605. Fax: (508) 856-6588. E-mail: elliot.androphy{at}umassmed.edu.

{dagger} Present address: PKC Corporation, Burlington, VT 05401.

Journal of Virology, November 2002, p. 11359-11364, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11359-11364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Johung, K., Goodwin, E. C., DiMaio, D. (2007). Human Papillomavirus E7 Repression in Cervical Carcinoma Cells Initiates a Transcriptional Cascade Driven by the Retinoblastoma Family, Resulting in Senescence. J. Virol. 81: 2102-2116 [Abstract] [Full Text]  
  • Oliveira, J. G., Colf, L. A., McBride, A. A. (2006). Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. USA 103: 1047-1052 [Abstract] [Full Text]  
  • Nakahara, T., Peh, W. L., Doorbar, J., Lee, D., Lambert, P. F. (2005). Human Papillomavirus Type 16 E1{wedge}E4 Contributes to Multiple Facets of the Papillomavirus Life Cycle. J. Virol. 79: 13150-13165 [Abstract] [Full Text]  
  • Lee, C., Laimins, L. A. (2004). Role of the PDZ Domain-Binding Motif of the Oncoprotein E6 in the Pathogenesis of Human Papillomavirus Type 31. J. Virol. 78: 12366-12377 [Abstract] [Full Text]  
  • Munger, K., Baldwin, A., Edwards, K. M., Hayakawa, H., Nguyen, C. L., Owens, M., Grace, M., Huh, K. (2004). Mechanisms of Human Papillomavirus-Induced Oncogenesis. J. Virol. 78: 11451-11460 [Full Text]  
  • Garner-Hamrick, P. A., Fostel, J. M., Chien, W.-M., Banerjee, N. S., Chow, L. T., Broker, T. R., Fisher, C. (2004). Global Effects of Human Papillomavirus Type 18 E6/E7 in an Organotypic Keratinocyte Culture System. J. Virol. 78: 9041-9050 [Abstract] [Full Text]  
  • Oh, S. T., Longworth, M. S., Laimins, L. A. (2004). Roles of the E6 and E7 Proteins in the Life Cycle of Low-Risk Human Papillomavirus Type 11. J. Virol. 78: 2620-2626 [Abstract] [Full Text]  
  • Tao, M., Kruhlak, M., Xia, S., Androphy, E., Zheng, Z.-M. (2003). Signals That Dictate Nuclear Localization of Human Papillomavirus Type 16 Oncoprotein E6 in Living Cells. J. Virol. 77: 13232-13247 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»