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Journal of Virology, September 1998, p. 7255-7262, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Interaction between the Bovine Papillomavirus Virus Type 1 Replicative Helicase E1 and Cyclin E-Cdk2dagger

Nathalie Cueille,1 Romain Nougarede,1,Dagger Francisca Mechali,1 Michel Philippe,2 and Catherine Bonne-Andrea1,*

Centre de Recherches de Biochimie Macromoléculaire, CNRS, UPR 1086, 34293 Montpellier Cedex 5,1 and Département de Biologie et Génétique du Développement, CNRS, URA 256, Université de Rennes I, Campus de Beaulieu, 35042 Rennes Cedex,2 France

Received 20 March 1998/Accepted 28 May 1998

We have found that the replicative helicase E1 of bovine papillomavirus type 1 (BPV-1) interacts with a key cell cycle regulator of S phase, the cyclin E-Cdk2 kinase. The E1 helicase, which interacts with cyclin E and not with Cdk2, presents the highest affinity for catalytically active kinase complexes. In addition, E1, cyclin E, and Cdk2 expressed in Xenopus egg extracts are quantitatively coimmunoprecipitated from crude extracts by either anti-Cdk2 or anti-E1 antibodies. E1 protein is also a substrate of the cyclin E-Cdk2 kinase in vitro. Using the viral components required for in vitro BPV-1 replication and free-membrane cytosol from Xenopus eggs, we show that efficient replication of BPV plasmids is dependent on the addition of E1-cyclin E-Cdk2 complexes. Thus, the BPV initiator of replication and cyclin E-Cdk2 are likely to function together as a protein complex which may be the key to the cell cycle regulation of papillomavirus replication.

* Corresponding author. Mailing address: Centre de Recherches de Biochimie Macromoléculaire, CNRS, UPR 1086, 1919 route de Mende, 34293 Montpellier Cedex 5, France. Phone: 33 4 67 61 33 32. Fax: 33 4 67 52 15 59. E-mail: catherin{at}crbm.cnrs-mop.fr.

dagger Dedicated to the memory of Jean-Claude Cavadore.

Dagger Present address: Institut de Génétique Moléculaire, CNRS, 34033 Montpellier, France.

Journal of Virology, September 1998, p. 7255-7262, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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