A Critical Role for p53 during the HPV16 Life Cycle
Christian T. Fontan, Claire D. James, Apurva T. Prabhakar, Molly L. Bristol, Raymonde Otoa, Xu Wang, Elmira Karimi, Pavithra Rajagopalan, Devraj Basu, Iain M. Morgan
Abstract
Human papillomaviruses are causative agents in around 5% of all cancers. There are currently no antivirals available to combat these infections and cancers, therefore it remains a priority to enhance our understanding of the HPV life cycle. Here, we demonstrate that an interaction between the viral replication/transcription/segregation factor E2 and the tumor suppressor p53 is critical for the HPV16 life cycle. HPV16 immortalized cells retain significant expression of p53, and the critical role for the E2-p53 interaction demonstrates why this is the case. If the E2-p53 interaction is disrupted then HPV16 immortalized cells fail to proliferate, have enhanced DNA damage and senescence, and there is premature differentiation during the viral life cycle. Results suggest that targeting the E2-p53 interaction would have therapeutic benefits, potentially attenuating the spread of HPV16.