Integrin alpha(v)beta(3) mediates rotavirus cell entry.
Rotavirus strains differ in their need for sialic acid (SA) for initial binding to the cell surface; however, the existence of a postattachment cell receptor, common to most, if not all, rotavirus strains, has been proposed. In the present study, antibodies to the alpha(v) and beta(3) integrin subunits, and the alpha(v)beta(3) ligand, vitronectin, efficiently blocked the infectivity of the SA-dependent rhesus rotavirus RRV, its SA-independent variant nar3, and the neuraminidase-resistant human rotavirus strain Wa. Vitronectin 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 shown to be 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 to all three rotavirus strains, and the increment of virus infectivity was reverted 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-resistant rotaviruses, and support the hypothesis that this integrin could determine, at least in part, the cellular susceptibility to rotaviruses.
Guerrero
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CA
Departamento de Genética y Fisiologia Molecular, Instituto de Biotecnologia, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62250, Mexico.
Méndez
E
E
Zárate
S
S
Isa
P
P
López
S
S
Arias
C F
CF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D009842:Oligopeptides / Q000378:metabolism; D038981:Receptors, Collagen; D011991:Receptors, Virus / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000276:immunology / Q000378:metabolism*; D012401:Rotavirus / Q000378:metabolism* / Q000502:physiology; D019096:Vitronectin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; D038981:Receptors, Collagen; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid