Roles of the E6 and E7 proteins in the life cycle of low-risk XXXX type 11.

@entity1 @entity1522 @entity1082 @entity9273
Many important functions have been attributed to the high-risk @entity1082 ) E6 and E7 proteins, including binding and degradation of p53 as well as interacting with Rb proteins. In contrast, the physiological roles of the low-risk E6 and E7 proteins remain unclear. Previous studies demonstrated that the high-risk E6 and E7 proteins also play roles in the productive life cycle by facilitating the maintenance of viral episomes (J. T. Thomas, W. G. Hubert, M. N. Ruesch, and L. A. Laimins, Proc. Natl. Acad. Sci. USA 96:8449-8454, 1999). In order to determine whether low-risk E6 or E7 is similarly necessary for the stable maintenance of episomes, @entity9273 ( @entity9273 ) genomes that contained translation termination mutations in E6 or E7 were constructed. Upon transfection into normal @entity1 keratinocytes, genomes in which E6 function was abolished were unable to be maintained episomally. Transfection of genomes containing substitution mutations in @entity1522 conserved in high- and low-risk HPV types suggested that multiple protein domains are involved in this process. Examination of cells transfected with @entity9273 genomes in which E7 function was inhibited were found to exhibit a more complex phenotype. At the second passage following transfection, mutant genomes were maintained as episomes but at significantly reduced levels than in cells transfected with the wild-type @entity9273 genome. Upon further passage in culture, however, the episomal forms of these E7 mutant genomes quickly disappeared. These findings identify important new functions for the low-risk E6 and E7 proteins in the episomal maintenance of low-risk @entity9273 genomes and suggest that they may act in a manner similar to that observed for the high-risk proteins.
