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Journal of Virology, December 2002, p. 11801-11808, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.11801-11808.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Amino Acid Residues in the Carboxy-Terminal Region of Cottontail Rabbit Papillomavirus E6 Influence Spontaneous Regression of Cutaneous Papillomas

Jiafen Hu,1 Nancy M. Cladel,1 Martin D. Pickel,1 and Neil D. Christensen1,2*

Department of Pathology, The Jake Gittlen Cancer Research Institute,1 Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania 170332

Received 24 May 2002/ Accepted 21 August 2002

Previous studies have identified two different strains of cottontail rabbit papillomavirus (CRPV) that differ by approximately 5% in base pair sequence and that perform quite differently when used to challenge New Zealand White (NZW) rabbit skin. One strain caused persistent lesions (progressor strain), and the other induced papillomas that spontaneously regressed (regressor strain) at high frequencies (J. Salmon, M. Nonnenmacher, S. Caze, P. Flamant, O. Croissant, G. Orth, and F. Breitburd, J. Virol. 74:10766-10777, 2000; J. Salmon, N. Ramoz, P. Cassonnet, G. Orth, and F. Breitburd, Virology 235:228-234, 1997). We generated a panel of CRPV genomes that contained chimeric and mutant progressor and regressor strain E6 genes and assessed the outcome upon infection of both outbred and EIII/JC inbred NZW rabbits. The carboxy-terminal 77-amino-acid region of the regressor CRPV strain E6, which contained 15 amino acid residues that are different from those of the equivalent region of the persistent CRPV strain E6, played a dominant role in the conversion of the persistent CRPV strain to one showing high rates of spontaneous regressions. In addition, a single amino acid change (G252E) in the E6 protein of the CRPV progressor strain led to high frequencies of spontaneous regressions in inbred rabbits. These observations imply that small changes in the amino acid sequences of papillomavirus proteins can dramatically impact the outcome of natural host immune responses to these viral infections. The data imply that intrastrain differences between separate isolates of a single papillomavirus type (such as human papillomavirus type 16) may contribute to a collective variability in host immune responses in outbred human populations.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, PA 17033. Phone: (717) 531-6185. Fax: (717) 531-6185. E-mail: ndc1{at}psu.edu.

Journal of Virology, December 2002, p. 11801-11808, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.11801-11808.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hu, J., Budgeon, L. R., Cladel, N. M., Culp, T. D., Balogh, K. K., Christensen, N. D. (2007). Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus. J. Gen. Virol. 88: 3286-3293 [Abstract] [Full Text]  
  • Hu, J., Peng, X., Budgeon, L. R., Cladel, N. M., Balogh, K. K., Christensen, N. D. (2007). Establishment of a Cottontail Rabbit Papillomavirus/HLA-A2.1 Transgenic Rabbit Model. J. Virol. 81: 7171-7177 [Abstract] [Full Text]  
  • Hu, J., Peng, X., Schell, T. D., Budgeon, L. R., Cladel, N. M., Christensen, N. D. (2006). An HLA-A2.1-Transgenic Rabbit Model to Study Immunity to Papillomavirus Infection. J. Immunol. 177: 8037-8045 [Abstract] [Full Text]  
  • Hu, J., Peng, X., Cladel, N. M., Pickel, M. D., Christensen, N. D. (2005). Large cutaneous rabbit papillomas that persist during cyclosporin A treatment can regress spontaneously after cessation of immunosuppression. J. Gen. Virol. 86: 55-63 [Abstract] [Full Text]  


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