Fig. 2.

HPV life cycle organization. The HPV life cycle is dependent on the terminal differentiation of the keratinocyte. The virus life cycle begins by the viral particle (red pentagon) gaining access to the basal lamina and then infecting the mitotically active basal keratinocyte. The viral genome (black circle) is established as an extra-chromosomal replicon and maintained in basal cells until the cell differentiates and HPV early protein expression increases. Differentiating cells are pushed back into cell cycle and the viral genome amplifies to high copy number. Finally, the cell completes differentiation, expresses the viral late structural proteins L1 and L2 enabling virion assembly and egress. A viral regulator E8^E2 regulates viral transcription and replication and can also inhibit its own promoter P_E8 suggesting that levels of the regulator may be finely tuned during the life cycle