Integrin αvβ35 selectively promotes adenovirus mediated cell membrane permeabilization

Abstract

Human adenovirus type 2 (Ad2) enters host cells by receptor-mediated endocytosis, an event mediated by the virus penton base binding to cell surface integrins αvβ3 and αvβ5. While both αv integrins promote virus internalization, αvβ5 is involved in the subsequent event of membrane permeabilization. Cells transfected with the β5 or β3 subunit, expressing either αvβ5 and αvβ3, respectively, were capable of supporting Ad2 infection to varying degrees. In this case, cells expressing αvβ5 were significantly more susceptible to Ad2-induced membrane permeabilization, as well as to Ad2 infection, than cells expressing αvβ3. Adenovirus-mediated gene delivery was also more efficient in cells expressing αvβ5. These results suggest that the interaction of αvβ5 with Ad2 penton base facilitates the subsequent step of virus penetration into the cell. These studies provide evidence for the involvement of a cellular receptor in virus-mediated membrane permeabilization and suggest a novel biological role for integrin αvβ5 in the infectious pathway of a human adenovirus.