The biology of human papillomaviruses.

Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that cause lesions in cutaneous and mucosal tissue and are responsible for carcinomas of the cervix, vagina, vulva and penis. HPVs sort into 5 genera with a total of approximately 150 species that have been sequenced. Its genome is comprised of an early (E) region encoding the viral regulatory proteins, a late (L) region encoding the viral structural proteins and a noncoding region that is essential to the viral life cycle. For infection to occur, the virus must access the basal epidermal layer where, following endocytosis and viral capsid disassembly, the L2 protein mediates viral genome transfer to the nuclei of mitotic keratinocytes. The viral genome is maintained in episomal form during the normal life cycle and replicates in synchrony with the host cell DNA under the mediation of E1, E2, E4 and E5 viral proteins. In most high-grade cervical neoplasms, however, the viral DNA is integrated into the host genome through the disruption of the E2 open reading frame. The oncoproteins E6 and E7, which were previously suppressed by E2, are then free to inhibit the Rb and p53 tumor suppressor pathways. The viral life cycle concludes with the packaging of the viral genome and virus release, which entails the E2-mediated recruitment of L2 to regions of replication, the expression of L1 and the assembly of the icosahedral capsid in the nucleus. Overall, the complex biology of HPV continues to be an important area of research with substantial implications for public health.