title: Rotavirus-neutralizing antibodies inhibit virus binding to integrins alpha 2 beta 1 and alpha 4 beta 1.
abstract: Rotavirus outer capsid proteins VP5(*), VP8(*) and VP7 elicit neutralizing, protective antibodies. The alpha 2 beta 1 integrin is a cellular receptor for rotavirus that is bound by VP5(*). Some rotaviruses also recognize the alpha 4 beta 1 integrin. In this study, the effects of antibodies to rotavirus on virus binding to recombinant alpha 2 beta 1 and alpha 4 beta 1 expressed on K562 cells were determined. All neutralizing monoclonal antibodies to VP5(*) tested (YO-2C2, 2G4, 1A10) and two to VP7 (RV-3:2, RV-4:2) inhibited rotavirus binding to alpha 2 beta 1. Rotavirus binding to alpha 4 beta 1 was reduced by 2G4 and neutralizing antibody F45:2, directed to VP7. However, a neutralizing antibody to VP8(*) (RV-5:2) and one to VP7 (RV-3:1) did not affect rotavirus binding to these integrins. Virus-cell binding was unaffected by non-neutralizing antibody RVA to the rotavirus inner capsid protein VP6. The attachment of human rotavirus strain Wa to these integrins was inhibited by infection sera with neutralizing activity collected from two children hospitalised with severe rotavirus gastroenteritis. A negative reference serum did not affect rotavirus-cell attachment. As the binding of rotaviruses to alpha 2 beta 1 and alpha 4 beta 1 is inhibited by neutralizing antibodies to VP5(*) and VP7, and serum from children with rotavirus disease, rotavirus recognition of these integrins may be important for host infection.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia.
authors.forename: F E
authors.initials: FE
authors.lastname: Fleming
authors.forename: K L
authors.initials: KL
authors.lastname: Graham
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: B S
authors.initials: BS
authors.lastname: Coulson
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D002460:Cell Line; D002648:Child; D005759:Gastroenteritis / Q000276:immunology / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D020014:K562 Cells; D009500:Neutralization Tests; D016601:RNA-Binding Proteins / Q000276:immunology; D012401:Rotavirus / Q000276:immunology* / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000276:immunology / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D038982:Integrin alpha2beta1; D039041:Integrin alpha4beta1; D016601:RNA-Binding Proteins; C050779:VP7 protein, Rotavirus; D017361:Viral Nonstructural Proteins; C104282:nsp1 protein, Rotavirus; C079234:NS35 protein, rotavirus