Initial steps and mechanisms of HPV infection

Human papillomaviruses are small, non-enveloped viruses. They have circular double-stranded DNA in an icosahedral capsid. Structural proteins of viral capsid, play important role in efficient virus infectivity. The viral L1 protein binds to the exposed basement membrane via heparan sulphate proteoglycans (primary receptor) and α6 integrin (secondary receptor). That binding triggers receptor mediated endocytosis of HPV. Most HPV types use clathrin dependent endocytic pathway. Clathrin coated vesicles uncoated after endocytosis and fuse with early endosomes. HPV can avoid lysosomal degradation. It can escape from the endosomes to the cytosol, with various mechanisms (membrane disruption, transmembrane pore formation, pH decline). Finally the complex of HPV genome and L2 protein enters the nucleus. Then, HPV transcription and replication occur in association with PML nuclear bodies. During latent infection, HPV genome maintain as autonomous replicating episome in the proliferating basal cells of the squamous epithelium