Integrin alpha(v)beta(3) mediates rotavirus cell entry

Rotavirus strains differ in their need for sialic acid (SA) for initial bin ding to the cell surface; however, the existence of a postattachment cell r eceptor, common to most, if not all, rotavirus strains, has been proposed. In the present study, antibodies to the alpha (v) and beta (3) integrin sub units, and the alpha (v)beta (3) ligand, vitronectin, efficiently blocked t he infectivity of the SA-dependent rhesus rotavirus RRV, its SA-independent variant nar3, and the neuraminidase-resistant human rotavirus strain Wa. V itronectin and anti-beta (3) antibodies, however, did not block the binding of virus to cells, indicating that rotaviruses interact with alpha (v)beta (3) at a postbinding step, probably penetration. This interaction was show n to he independent of the tripeptide motif arginine-glycine-aspartic acid present in the natural ligands of this integrin. Transfection of CHO cells with alpha (v)beta (3) genes significantly increased their permissiveness t o all three rotavirus strains, and the increment of virus infectivity was r everted by incubation of these cells either with antibodies to beta (3) or with vitronectin. These findings implicate alpha (v)beta (3) integrin as a cellular receptor common to neuraminidase-sensitive and neuraminidase-resis tant rotaviruses, and support the hypothesis that this integrin could deter mine, at least in part, the cellular susceptibility to rotaviruses.