The bovine papillomavirus E1 protein alters the host cell cycle and growth properties

A stable E1-expressing cell line, CE1, was developed to investigate the effect of bovine papillomavirus E1 protein on host cell growth. Expression of E1 in CE1 cells is under control of the dexamethasone-inducible mouse mammary tumor virus LTR promoter. Flow cytometry was used to determine the intracellular levels of E1 in CE1 cells in parallel with cell cycle distributions and cell growth parameters. CE1 cells expressed a basal level of E1 that was increased following exposure to increasing concentrations of dexamethasone. As E1 expression increased, the following effects on cell growth were observed: (1) the overall cell generation time increased and (2) the duration of G1 + G0 phases increased slightly while the duration of G2 + M phases increased twofold. The appearance of a cell subpopulation with a greater than G2 phase DNA content was also observed in E1-expressing cells. Removal of dexamethasone resulted in a return of E1 levels to the basal state with a concomitant restoration of both cell growth properties and cell cycle phase distributions. All of the observed effects were seen in the absence of both other papillomaviral proteins and papillomaviral DNA replication. We conclude that E1 is sufficient to negatively affect host cell growth, with a prominent effect observed in the G2 + M phases.