AN INTERACTION BETWEEN PENTON BASE AND ALPHA-V INTEGRINS PLAYS A MINIMAL ROLE IN ADENOVIRUS-MEDIATED GENE-TRANSFER TO HEPATOCYTES IN-VITRO AND IN-VIVO

Studies in cultured cell lines have shown that adenovirus infection in volves binding of adenovirus fiber to ifs cell sur: face receptor and binding of penton base to cuv integrins. However, much less is known a bout the role of these interactions in cells that are targets for aden ovirus-mediated gene transfer Earlier work showed that hepatocytes are readily infected by adenovirus, making them an attractive target for gene therapy in several diseases. We found that addition of fiber prot ein blocked adenovirus infection of primary cultures of hepatocytes. T his suggests an important role for fiber and its receptor. However, mu tation of the integrin-binding motif in penton base did not inhibit in fection of hepatocytes, even though the mutation impaired infection of HeLa cells. Hepatocytes had undetectable amounts of alpha V integrins an heir cell surface and showed. no specific adherence to vitronectin , the natural substrate of alpha V integrins. Adenovirus with an intac t penton base enhanced infection of liver following intravenous inject ion, but only by three-fold as compared with virus in which the integr in-binding motif was disrupted. These studies suggest that interaction s between cell surface integrins and penton base are not required for adenovirus infection of hepatocytes in vitro, but the interaction enha nces infection to a small degree in vivo.