Fig. 1

Organization of HPV genome. a. HPV genome has a circular double-stranded DNA (8000bp). The viral genes are transcribed in a single direction (clockwise). There are genes coding for non-structural proteins (E1, E2, E4, E5, E6, and E7) and structural proteins (L1, L2), and a transcriptional control region (long control region; LCR). LCR contains a DNA replication origin and functions as a regulator for DNA replication. b. The HPV lifecycle. Human papillomavirus is thought to reach the basal cells through microabrasions in the cervical epithelium. After infection, the early human papillomavirus genes E1, E2, E4, E5, E6, and E7 are expressed and the viral DNA replicates from episomal DNA and establishes ∼50 HPV episome copies, which then segregate between the daughter progeny as the cells undergo cell division. In the upper layers of epithelium, viral genome is replicated further, and late genes L1 and L2, and E4 are expressed. The early viral proteins E6 and E7 are key to stimulating proliferation and milieu for E1 and E2-driven viral genome replication to a high copy number. Integration of human papillomavirus genome into the host chromosome occurs with associated loss or disruption of E2, and subsequent upregulation of E6 and E7 oncogene expression. Terminal differentiation of infected cells in the upper epithelial layers activates the expression of E4 and then L1 and L2 to encapsidate the viral genomes to form progeny virions. The shed virus can then initiate a new infection