Figure 1.

Mechanisms for formation of viral–human hybrid episomes. In (A), a human papillomavirus 16 (HPV16) dimer has broken and integrated into the host genome, losing a part of one of the viral genomes as often happens during integration. E1 and E2 can still be expressed from the intact HPV genome and therefore the potential to initiate replication from the viral origins is retained; this initiation is not restricted to once per cell cycle therefore repeated initiation would form an “onion skin” replication bubble. This would create stress on the host genome resulting in double strand breaks promoting excision from the host genome. This viral–human hybrid DNA could then be ligated to form an episome. In (B), the breaks occur in the host genome flanking the integrated viral genome (the green arrows) and ligation occurs to form an episome that consists of the viral genome with two flanking regions of human DNA. In (C) the breaks in the DNA occur in the viral genome and in flanking human DNA (orange arrows) and ligation occurs to form a viral–human hybrid episome that consists of the viral genome with one flanking region of human DNA. LCR = long control region.