Fig. 1

(a) Membrane raft structure. (b) 1: Heparin sulfate proteoglycans (HSPGs) on the surface of epithelial cells, the basement membrane, or the extracellular matrix (ECM) are bound by HPV-16 via laminin-332. Now, HSPG/growth factor HPV-16 complexes may also promote the activation of the EGFR and KGFR receptors on keratinocytes, which might result in intracellular signaling cascades that activate the PI3K pathway and other signaling pathways. 2: After the virion binds to HSPGs, cyclophilin B (CyPB) helps it undergo a conformational shift that increases the number of amino acids from the L2 N terminus that are exposed. The next step is for HPV-16 to bind to α6 integrin, which starts an intracellular signaling cascade. 3: After conformational alterations and signaling, the HPV-16 capsid attaches itself to A2t. After attaching to the A2t, HPV-16 proceeds through endocytosis without the presence of clathrin, caveolin, lipid raft, flotillin, CHO, or dynamin. Actin scission and vesicle closure may be following processes involving PI3K activation brought on by HPV-16. Tetraspanins are thought to have a role in the development of an enriched membrane domain that preserves the integrity of the bonds separating molecules linked to HPV-16. Adam B Raff and colleagues propose that HSPGs, CyPB, α6 integrin, tetraspanins, EGFR, and A2t form a receptor complex, as opposed to the virion transferring sequentially from one receptor to another [46]