19 Review HJOG An Obstetrics and Gynecology International Journal VOLUME 14, ISSUE 1, JANUARY - MARCH 2015 Τ he infectious cycle of human papilloma virus (HPV) is entirely carried out in a fully differen- tiated squamous epithelium 1 . It is essential that the virus particles gain access to the basal layer of the epithelium and enter to the dividing basal cells 2 . For this purpose, a micro - abrasion of the epithelial sur- face is necessary, which removes the epithelium but retains intact with its basement membrane. Meta- plastic epithelium is thinner, more fragile and may be more susceptible to the micro - abrasion process and the HPV infection 1 . Viral structure HPVs are small, non - enveloped viruses 1 . They have circular double - stranded DNA in an icosahedral capsid 2 . They are completely species and tissue spe- cific. Their genome usually contains around 8,000 bp and encodes 8 or 9 ORFs (open reading frames) 2 . They have very complex molecular biology, despite their small size 3 . Viral capsid is composed by 2 struc- tural proteins (L1 and L2) 3-5 . Moreover, structural proteins play important role in efficient virus infec- tivity 2 . Also, HPVs have 3 oncogenes (E5, E6 and E7) and 2 regulatory proteins (E1 and E2). Oncogenes modulate the transformation process. Regulatory proteins modulate transcription and replication 3,4 . Binding on cell surface receptors The viral L1 protein binds to the exposed basement membrane probably via heparan sulphate proteogly- Initial steps and mechanisms of HPV infection Androutsopoulos Georgios, Thanatsis Nikolaos, Michail Georgios, Adonakis Georgios, Decavalas Georgios Department of Obstetrics and Gynecology, University of Patras, Medical School, Rio, Greece Correspondence Androutsopoulos Georgios Department of Obstetrics and Gynecology, University of Patras, Medical School, Rio, GR-26504, Greece E - mail: androutsopoulosgeorgios@hotmail.com Human papillomaviruses (HPV) are small, non-envel- oped viruses. They have circular double-stranded DNA in an icosahedral capsid. Structural proteins of viral cap- sid, play important role in efcient virus infectivity. The viral L1 protein binds to the exposed basement mem- brane via heparan sulphate proteoglycans (primary re- ceptor) and α6 integrin (secondary receptor). That bind- ing triggers receptor mediated endocytosis of HPV. Most HPV types use clathrin dependent endocytic pathway. Clathrin coated vesicles become uncoated after endocy- tosis and fuse with early endosomes. HPV can avoid lys- osomal degradation and escape from the endosomes to the cytosol, with various mechanisms, including mem- brane disruption, transmembrane pore formation and pH decline. Finally, the complex of HPV genome and L2 protein enters the nucleus. Then, HPV transcription and replication occur in association with promyelocyt- ic leukemia (PML) nuclear bodies. During latent infec- tion, HPV genome maintain as autonomous replicating episome in the proliferating basal cells of the squamous epithelium. Key words: molecular biology; HPV; infection; receptors; endocytosis; intracellular trafcking; nuclear entry Abstract