Fig. 1.

Papillomavirus life cycle. Viral lodgment starts from tissue micro-injury (because these viruses cannot actively penetrate the skin of their host), but other routes were reported as infected lymphocytes (viral hematogenous infection to the skin or urinary bladder), infected semen, and infected milk. After tissue micro-injury, heparin sulfate proteoglycan (HSPG) receptors that present on the basement membrane (BM) provides access to the basal keratinocytes, are exposed to L1 binding leading to conformational changes in capsid icosahedral structure, exposing the L2 N-terminal to be cleaved by extracellular furin protein that presents in the cell membrane inducing a second capsid conformational change, allowing L2 to bind to different receptors, such as integrin 24. Viral entry; virions internalization by clathrin-dependent endocytosis mechanism, resulting in cytoplasmic vesicles that associate to lysosomes, the lysosomal acid content release promotes pH alterations in capsid proteins, resulting in viral DNA release. BPV genome is found in episomal form and HPV genome can integrate into fragile sites of the host genome. Differentiation triggers the production of the PV early proteins that force the suprabasal cell to reenter the S-phase of the cell cycle resulting in cell cycle continuation. Amplification process: PVs induce the S-phase entry because they do not codify polymerase, stimulating cell proliferation, and inducing mitotic stress. As a result, many cell cycle checkpoints are abrogated. Consequently, an accumulation of mutations resulting in cytogenetic aberrations and progression into cancer occurs in cells that are persistently infected by these viruses. The productive infection occurs within the terminal differentiation and keratinization of an infected cell. PV late genes expression and viral assembly occur close to the cell surface and viral particles are released only after the epithelial cell sloughing from the epithelial surface and not by causing cell lysis. Thus, the viral life cycle is completed without directly causing cell death and without systemic viremia