Properties of bovine papillomavirus E1 mutants

Ostensibly comparable mutants of bovine papillomavirus type 1 (BPV-1) affecting the E1 open reading frame that were constructed in several laboratories have been reported to exhibit either reduced or increased transformation efficiencies in established mouse cell lines relative to wild-type BPV-1 DNA. To resolve these discrepancies, we have reexamined many of the mutants in mouse C127 cells by using focus formation assays. Our primary conclusions are that all E1 mutants tested consistently generated reduced numbers of transformants and that the reduced transformation was not due to cell toxicity associated with E1 mutations, as had been proposed. Our results can best be explained by the inability of the E1 mutants to replicate extrachromosomally, therefore leading to a rapid loss of the BPV-1 DNA and consequently, reduced transformation. In support of this hypothesis, we demonstrated that the human papillomavirus type 11 E1 protein was able to suppress BPV-1 transformation, probably because of interference with BPV-1 replication. Therefore, we attribute the phenotypic disparities reported by the various laboratories to still undefined differences in assay conditions.