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 Kasukawa, H.
Right arrow Articles by Benson, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kasukawa, H.
Right arrow Articles by Benson, J. D.

 Previous Article  |  Next Article 

Journal of Virology, October 1998, p. 8166-8173, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Fifteen-Amino-Acid Peptide Inhibits Human Papillomavirus E1-E2 Interaction and Human Papillomavirus DNA Replication In Vitro

Hiroaki Kasukawa, Peter M. Howley, and John D. Benson*

Department of Pathology, Harvard Medical School, Boston, Massachusetts

Received 3 June 1998/Accepted 10 July 1998

Mutation of the conserved glutamic acid residue at position 39 of human papillomavirus type 16 (HPV-16) E2 to alanine (E39A) disrupts its E1 interaction activity and its replication function in transient replication assays but does not affect E2 transcriptional activation. This E39A mutation also disrupts replication activity of HPV-16 E2 in HPV-16 in vitro DNA replication. On this basis, we designed 23- and 15-amino-acid peptides derived from HPV-16 E2 sequences flanking the E39 residue and tested the ability of these peptides to inhibit interaction between HPV-16 E1 and E2 in vitro. The inhibitory activity of these peptides was specific, since analogous peptides in which alanine was substituted for the E39 residue did not inhibit interaction. The 15-amino-acid peptide E2N-WP15 was the smallest peptide tested that effectively inhibited HPV-16 E1-E2 interaction. This peptide also inhibited in vitro replication of HPV-16 DNA. The efficacy of E2N-WP15 was not exclusive to HPV-16: this peptide also inhibited interaction of HPV-11 E1 with the E2 proteins of both HPV-11 and HPV-16 and inhibited in vitro replication with these same combinations of E1 and E2 proteins. These results provide further evidence that E1-E2 interaction is required for papillomavirus DNA replication and constitute the first demonstration that inhibition of this interaction is sufficient to prevent HPV DNA replication in vitro.

* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-2892. Fax: (617) 432-0727. E-mail: jbenson{at}warren.med.harvard.edu.

Journal of Virology, October 1998, p. 8166-8173, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Deng, S.-J., Pearce, K. H., Dixon, E. P., Hartley, K. A., Stanley, T. B., Lobe, D. C., Garvey, E. P., Kost, T. A., Petty, R. L., Rocque, W. J., Alexander, K. A., Underwood, M. R. (2004). Identification of Peptides That Inhibit the DNA Binding, trans-Activator, and DNA Replication Functions of the Human Papillomavirus Type 11 E2 Protein. J. Virol. 78: 2637-2641 [Abstract] [Full Text]  
  • Fujii, T., Austin, D., Guo, D., Srimatkandada, S., Wang, T., Kubushiro, K., Masumoto, N., Tsukazaki, K., Nozawa, S., Deisseroth, A. B. (2003). Peptides Inhibitory for the Transcriptional Regulatory Function of Human Papillomavirus E2. Clin. Cancer Res. 9: 5423-5428 [Abstract] [Full Text]  
  • White, P. W., Titolo, S., Brault, K., Thauvette, L., Pelletier, A., Welchner, E., Bourgon, L., Doyon, L., Ogilvie, W. W., Yoakim, C., Cordingley, M. G., Archambault, J. (2003). Inhibition of Human Papillomavirus DNA Replication by Small Molecule Antagonists of the E1-E2 Protein Interaction. J. Biol. Chem. 278: 26765-26772 [Abstract] [Full Text]  
  • Nishimura, A., Ono, T., Ishimoto, A., Dowhanick, J. J., Frizzell, M. A., Howley, P. M., Sakai, H. (2000). Mechanisms of Human Papillomavirus E2-Mediated Repression of Viral Oncogene Expression and Cervical Cancer Cell Growth Inhibition. J. Virol. 74: 3752-3760 [Abstract] [Full Text]  
  • Vance, K. W., Campo, M. S., Morgan, I. M. (1999). An Enhanced Epithelial Response of a Papillomavirus Promoter to Transcriptional Activators. J. Biol. Chem. 274: 27839-27844 [Abstract] [Full Text]  
  • Titolo, S., Pelletier, A., Sauvé, F., Brault, K., Wardrop, E., White, P. W., Amin, A., Cordingley, M. G., Archambault, J. (1999). Role of the ATP-Binding Domain of the Human Papillomavirus Type 11 E1 Helicase in E2-Dependent Binding to the Origin. J. Virol. 73: 5282-5293 [Abstract] [Full Text]  
  • Harris, S. F., Botchan, M. R. (1999). Crystal Structure of the Human Papillomavirus Type 18 E2 Activation Domain. Science 284: 1673-1677 [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»