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Journal of Virology, February 2004, p. 2142-2151, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.2142-2151.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Viral E4 Protein Is Required for the Completion of the Cottontail Rabbit Papillomavirus Productive Cycle In Vivo

Woei L. Peh,1 Janet L. Brandsma,2 Neil D. Christensen,3 Nancy M. Cladel,3 Xing Wu,2 and John Doorbar1*

Division of Virology, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom,1 Section of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510,2 Department of Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania 170333

Received 18 August 2003/ Accepted 30 October 2003

Expression of the papillomavirus E4 protein correlates with the onset of viral DNA amplification. Using a mutant cottontail rabbit papillomavirus (CRPV) genome incapable of expressing the viral E4 protein, we have shown that E4 is required for the productive stage of the CRPV life cycle in New Zealand White and cottontail rabbits. In these lesions, E4 was not required for papilloma development, but the onset of viral DNA amplification and L1 expression were abolished. Viral genome amplification was partially restored when mutant genomes able to express longer forms of E4 were used. These findings suggest that efficient amplification of the CRPV genome is dependent on the expression of a full-length CRPV E4 protein.

* Corresponding author. Mailing address: The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 20 8816 2623. Fax: 44 20 8906 4477. E-mail: jdoorba{at}nimr.mrc.ac.uk.

Journal of Virology, February 2004, p. 2142-2151, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.2142-2151.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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