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Journal of Virology, June 2006, p. 5405-5412, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.01795-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of DNA Replication of Human Papillomavirus by Artificial Zinc Finger Proteins

Takashi Mino, Takeaki Hatono, Naoki Matsumoto, Tomoaki Mori, Yusuke Mineta, Yasuhiro Aoyama,* and Takashi Sera*

Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan

Received 24 August 2005/ Accepted 6 March 2006

Recently, we demonstrated that plant DNA virus replication was inhibited in planta by using an artificial zinc finger protein (AZP) and created AZP-based transgenic plants resistant to DNA virus infection. Here we apply the AZP technology to the inhibition of replication of a mammalian DNA virus, human papillomavirus type 18 (HPV-18). Two AZPs, designated AZPHPV-1 and AZPHPV-2, were designed by using our nondegenerate recognition code table and were constructed to block binding of the HPV-18 E2 replication protein to the replication origin. Both of the newly designed AZPs had much higher affinities towards the replication origin than did the E2 protein, and they efficiently blocked E2 binding in vitro. In transient replication assays, both AZPs inhibited viral DNA replication, especially AZPHPV-2, which reduced the replication level to approximately 10%. We also demonstrated in transient replication assays, using plasmids with mutant replication origins, that AZPHPV-2 could precisely recognize the replication origin in mammalian cells. Thus, it was demonstrated that the AZP technology could be applied not only to plant DNA viruses but also to mammalian DNA viruses.

* Corresponding author. Mailing address: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigaku-Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan. Phone for Takashi Sera: 81-75-383-2769. Fax: 81-75-383-2767. E-mail:sera{at}sbchem.kyoto-u.ac.jp. Phone for Yasuhiro Aoyama: 81-75- 383-2766. Fax: 81-75-383-2767. E-mail: aoyamay{at}sbchem.kyoto-u.ac.jp.

Journal of Virology, June 2006, p. 5405-5412, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.01795-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Horner, S. M., DiMaio, D. (2007). The DNA Binding Domain of a Papillomavirus E2 Protein Programs a Chimeric Nuclease To Cleave Integrated Human Papillomavirus DNA in HeLa Cervical Carcinoma Cells. J. Virol. 81: 6254-6264 [Abstract] [Full Text]  


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