title: Integrin alphavbeta8 functions as a receptor for foot-and-mouth disease virus: role of the beta-chain cytodomain in integrin-mediated infection.
abstract: Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use three alphav integrins, alphavbeta1, alphavbeta3, and alphavbeta6, as cellular receptors. Binding to the integrin is mediated by a highly conserved RGD motif located on a surface-exposed loop of VP1. The RGD tripeptide is recognized by several other members of the integrin family, which therefore have the potential to act as receptors for FMDV. Here we show that SW480 cells are made susceptible to FMDV following transfection with human beta8 cDNA and expression of alphavbeta8 at the cell surface. The involvement of alphavbeta8 in infection was confirmed by showing that virus binding and infection of the transfected cells are inhibited by RGD-containing peptides and by function-blocking monoclonal antibodies specific for either the alphavbeta8 heterodimer or the alphav chain. Similar results were obtained with a chimeric alphavbeta8 including the beta6 cytodomain (alphavbeta8/6), showing that the beta6 cytodomain can substitute efficiently for the corresponding region of beta8. In contrast, virus binding to alphavbeta6 including the beta8 cytodomain (alphavbeta6/8) was lower than that of the wild-type integrin, and this binding did not lead to infection. Further, the alphavbeta6 chimera was recognized poorly by antibodies specific for the ectodomain of alphavbeta6 and displayed a relaxed sequence-binding specificity relative to that of wild-type integrin. These data suggest that the beta6 cytodomain is important for maintaining alphavbeta6 in a conformation required for productive infection by FMDV.
authors.affiliation: Department of Molecular Biology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom. terry.jackson@bbsrc.ac.uk
authors.forename: Terry
authors.initials: T
authors.lastname: Jackson
authors.forename: Stuart
authors.initials: S
authors.lastname: Clark
authors.forename: Stephen
authors.initials: S
authors.lastname: Berryman
authors.forename: Alison
authors.initials: A
authors.lastname: Burman
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cambier
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
authors.forename: Stephen
authors.initials: S
authors.lastname: Nishimura
authors.forename: Andrew M Q
authors.initials: AM
authors.lastname: King
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005434:Flow Cytometry; D029544:Foot-and-Mouth Disease Virus / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D016023:Integrins; D011991:Receptors, Virus; C403414:integrin alphavbeta8