INTEGRIN-ALPHA-V-BETA-3 AND INTEGRIN-ALPHA-V-BETA-5 PROMOTE ADENOVIRUS INTERNALIZATION BUT NOT VIRUS ATTACHMENT

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 infect ion. We demonstrate that the vitronectin-binding integrins alpha(v)bet a3 and alpha(v)beta5 promote viral infection in a novel way since anti bodies against these receptors or soluble penton base block virus inte rnalization without affecting attachment. Moreover, adenovirus binds t o cultured cells lacking alpha(v) integrins but fail to become interna lized, thus restricting infection of these cells. Transfection of alph a(v)(-) cells with a cDNA encoding alpha(v) results in the expression of integrins alpha(v)beta3 and alpha(v)beta5 and allows virus internal ization 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 f or attachment and alpha(v) integrin receptors for internalization.