(a) Adenoviral (Ad) attachment and internalisation is mediated through the knob protein of the fiber binding to CAR, followed by interaction of the penton base at the base of the fiber shaft with αv integrins on the cell
surface. Following internalisation, the virus is localised within cellular endosomes which upon acidification allows the virions to escape and traffic to the nucleus. Ad-mediated infection is therefore, dependent on levels of CAR with hepatocytes being highly permissive as shown with reasonable levels of transduction in endothelial cells (EC). (b) AAV2 binds to the primary receptor heparin sulfate proteoglycan (HSPG) on the cell surface and internalization is assisted by the secondary receptors αvβ5 integrins and fibroblast growth factor receptor 1. Transduction of vascular cell, in particular EC, is very poor compared with permissive cell types such as HeLa. Transduction of both cell types with rAAV2-eGFP clearly shows the difference in transduction efficiency.