Comparative analysis of the intracellular location of the high- and low-risk human papillomavirus oncoproteins.

We have compared the intracellular location of the HPV E6 and E7 proteins from high- and low-risk virus types. While high-risk HPV E7 displays diffuse nuclear expression, low-risk E7 has a nuclear punctuate pattern of expression. Similarly, while high-risk E6 is expressed throughout the cell, low-risk E6 is again predominantly nuclear with a punctuate pattern of expression. Both low-risk viral oncoproteins show colocalization with PML, whereas high-risk viral proteins do not. Finally, inhibition of the proteasome pathway results in a dramatic nuclear accumulation of high-risk E6 protein. These results demonstrate fundamental differences in the localization of these viral oncoproteins within the cell and offer alternative explanations for their respective differences in pathology.