NATURAL VARIANTS OF THE HUMAN PAPILLOMAVIRUS TYPE-16 E6 PROTEIN DIFFER IN THEIR ABILITIES TO ALTER KERATINOCYTE DIFFERENTIATION AND TO INDUCE P53 DEGRADATION

Three naturally occurring variant human papillomavirus type 16 (HPV-16 ) E6 proteins, which contained amino acid substitutions predominantly near the N terminus, exhibited significant differences in their abilit ies to abrogate keratinocyte differentiation in response to serum and calcium and to induce the degradation of p53 in vitro. One variant sur passed the reference E6 protein in its ability to abrogate keratinocyt e differentiation responses, whereas another showed a reduction in thi s activity. Interestingly, the biological activities of the HPV-16 E6 proteins and their abilities to induce p53 degradation in vitro were d irectly correlated. These results demonstrate that naturally occurring variants of HPV-16 differ in biological and biochemical properties wh ich might result in differences in pathogenicity.