THE BOVINE PAPILLOMAVIRUS E1 PROTEIN ALTERS THE HOST-CELL CYCLE AND GROWTH-PROPERTIES

A stable E1-expressing cell line, CE1, was developed to investigate th e effect of bovine papillomavirus E1 protein on host cell growth. Expr ession of E1 in CE1 cells is under control of the dexamethasone-induci ble mouse mammary tumor virus LTR promoter. Flow cytometry was used to determine the intracellular levels of E1 in CE1 cells in parallel wit h cell cycle distributions and cell growth parameters. CE1 cells expre ssed a basal level of E1 that was increased following exposure to incr easing concentrations of dexamethasone. As E1 expression increased, th e following effects on cell growth were observed: (1) the overall cell generation time increased and (2) the duration of G1 + G0 phases incr eased slightly while the duration of G2 + M phases increased twofold. The appearance of a cell subpopulation with a greater than G2 phase DN A content was also observed in E1-expressing cells. Removal of dexamet hasone resulted in a return of E1 levels to the basal state with a con comitant restoration of both cell growth properties and cell cycle pha se distributions. All of the observed effects were seen in the absence of both other papillomaviral proteins and papillomaviral DNA replicat ion. We conclude that E1 is sufficient to negatively affect host cell growth, with a prominent effect observed in the G2 + M phases. (C) 199 4 Academic Press, Inc.