title: Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment.
abstract: Adenovirus contains a heterodimeric protein complex consisting of 186 kd fiber protein that mediates high affinity virus attachment to cells and a 400 kd pentavalent subunit (penton base) that contains five Arg-Gly-Asp sequences, implying a role for integrins in adenovirus infection. We demonstrate that the vitro-nectin-binding integrins alpha v beta 3 and alpha v beta 5 promote viral infection in a novel way since antibodies against these receptors or soluble penton base block virus internalization without affecting attachment. Moreover, adenovirus binds to cultured cells lacking alpha v integrins but fail to become internalized, thus restricting infection of these cells. Transfection of alpha v(-) cells with a cDNA encoding alpha v results in the expression of integrins alpha v beta 3 and alpha v beta 5 and allows virus internalization and infection. These data indicate that adenovirus attachment and uptake into cells are separate but cooperative events that result from the interaction of distinct viral coat proteins with a receptor for attachment and alpha v integrin receptors for internalization.
authors: Scripps Research Institute, Department of Immunology, La Jolla, California 92037.
authors: T J
authors: TJ
authors: Wickham
authors: P
authors: P
authors: Mathias
authors: D A
authors: DA
authors: Cheresh
authors: G R
authors: GR
authors: Nemerow
mesh_terms: D000260:Adenoviruses, Human / Q000378:metabolism*; D000595:Amino Acid Sequence; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D002448:Cell Adhesion; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D016023:Integrins; D009842:Oligopeptides; D011991:Receptors, Virus; C043322:penton protein, adenovirus; C047981:arginyl-glycyl-aspartic acid