Figure 4.

A Model regulation of HPV copy number during the viral lifecycle. The yellow circle represents the viral episomes. During the maintenance phase, expression of E6 and E7 induces proliferation of basal keratinocytes and the viral genome is replicated extrachromosomally at low-copy number (1-10 copies per cell). Little if any E1 and E2 protein is expressed in the basal layer cells, which leads to theta-form replication of HPV genomes. As the cells differentiate, expression of E1 and E2 trans-factors increases in the spinous layer. A transition from theta to rolling circle replication results in an increase in copy number up to 100-1000 copies per cell. Post-amplification, high levels of L1 and L2 capsid genes are expressed and capsid assembly occurs in the granular and squamous layers of the stratified epithelium. Progeny virus is released by desquamation.