Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization.
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 alpha v beta 3 and alpha v beta 5. While both alpha v integrins promote virus internalization, alpha v beta 5 is involved in the subsequent event of membrane permeabilization. Cells transfected with the beta 5 or beta 3 subunit, expressing either alpha v beta 5 and alpha v beta 3, respectively, were capable of supporting Ad2 infection to varying degrees. In this case, cells expressing alpha v beta 5 were significantly more susceptible to Ad2-induced membrane permeabilization, as well as to Ad2 infection, than cells expressing alpha v beta 3. Adenovirus-mediated gene delivery was also more efficient in cells expressing alpha v beta 5. These results suggest that the interaction of alpha v beta 5 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 alpha v beta 5 in the infectious pathway of a human adenovirus.
Wickham
T J
TJ
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Filardo
E J
EJ
Cheresh
D A
DA
Nemerow
G R
GR
D000260:Adenoviruses, Human / Q000502:physiology*; D001386:Azides; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D002448:Cell Adhesion; D002460:Cell Line; D002463:Cell Membrane Permeability; D004705:Endocytosis; D015870:Gene Expression; D005966:Glucuronidase / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D016024:Receptors, Cytoadhesin / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins / Q000235:genetics; D019810:Sodium Azide; D014162:Transfection
D001386:Azides; D036022:Capsid Proteins; D016023:Integrins; D016024:Receptors, Cytoadhesin; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C064660:integrin alphaVbeta5; C043322:penton protein, adenovirus; D019810:Sodium Azide; D005966:Glucuronidase