Description
HPV is a double-stranded DNA virus with a circular genome that encodes early genes, including E1, E2, E4, E5, E6, and E7, essential for replication, transcription, and transformation, and late genes L1 and L2, encoding viral capsid proteins. The replication cycle of HPV is tightly linked to the differentiation of the infected epithelium. Indeed, viral protein production and virus assembly occur only in the upper differentiated layers of the epithelium. In the basal layer, HPV particles initially interact with the basement membrane mostly through heparan sulfate proteoglycans (HSPGs)—capsid L1 contacts, and subsequently bind to HSPGs present on the basal keratinocyte cell surface. This attachment triggers conformational changes in the L2 capsid protein, resulting in exposure of a consensus cleavage site in the L2 N-terminus, whose proteolysis facilitates further interaction of the viral capsid with secondary receptor(s) present on the keratinocyte membrane. After such binding, HPVs are generally internalized by clathrin-dependent endocytosis, which initially relies on actin-rich cell protrusions, acting as the transport mechanism along the endocytic machinery