PAPILLOMA FORMATION BY COTTONTAIL RABBIT PAPILLOMAVIRUS REQUIRES E1 AND E2 REGULATORY GENES IN ADDITION TO E6 AND E7 TRANSFORMING GENES

The present study used the cottontail rabbit papillomavirus DNA-rabbit system to evaluate whether the regulatory genes E1 and E2 and the tra nsforming gene E6 are required for papilloma formation. Frameshift mut ations were generated in the individual genes in the context of a full -length cottontail rabbit papillomavirus genome, and the mutant DNAs w ere intradermally inoculated into domestic rabbits. None of the mutant s induced papillomas. Marker rescue experiments confirmed that the def ects were due to mutations that we deliberately introduced. Marker res cue also confirmed our previous report that the upstream region of E7 around position 9 was critical for papilloma induction. These results demonstrate that the E1 and E2 regulatory genes as well as the E6 and E7 transforming genes are each required for papilloma formation. Each gene may provide molecular targets for therapeutic intervention.