title: Guinea pig-adapted foot-and-mouth disease virus with altered receptor recognition can productively infect a natural host.
abstract: We report that adaptation to infect the guinea pig did not modify the capacity of foot-and-mouth disease virus (FMDV) to kill suckling mice and to cause an acute and transmissible disease in the pig, an important natural host for this pathogen. Adaptive amino acid replacements (I(248)-->T in 2C, Q(44)-->R in 3A, and L(147)-->P in VP1), selected upon serial passages of a type C FMDV isolated from swine (biological clone C-S8c1) in the guinea pig, were maintained after virus multiplication in swine and suckling mice. However, the adaptive replacement L(147)-->P, next to the integrin-binding RGD motif at the GH loop in VP1, abolished growth of the virus in different established cell lines and modified its antigenicity. In contrast, primary bovine thyroid cell cultures could be productively infected by viruses with replacement L(147)-->P, and this infection was inhibited by antibodies to alphavbeta6 and by an FMDV-derived RGD-containing peptide, suggesting that integrin alphavbeta6 may be used as a receptor for these mutants in the animal (porcine, guinea pig, and suckling mice) host. Substitution T(248)-->N in 2C was not detectable in C-S8c1 but was present in a low proportion of the guinea pig-adapted virus. This substitution became rapidly dominant in the viral population after the reintroduction of the guinea pig-adapted virus into pigs. These observations illustrate how the appearance of minority variant viruses in an unnatural host can result in the dominance of these viruses on reinfection of the original host species.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Cantoblanco, 28049 Madrid, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: Núñez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molina
authors.forename: Eric
authors.initials: E
authors.lastname: Baranowski
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
authors.forename: Stuart
authors.initials: S
authors.lastname: Clark
authors.forename: Alison
authors.initials: A
authors.lastname: Burman
authors.forename: Stephen
authors.initials: S
authors.lastname: Berryman
authors.forename: Terry
authors.initials: T
authors.lastname: Jackson
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D000833:Animals, Suckling; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D005536:Foot-and-Mouth Disease / Q000635:transmission*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000472:pathogenicity*; D006168:Guinea Pigs / Q000821:virology*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011991:Receptors, Virus / Q000378:metabolism; D013552:Swine / Q000821:virology*
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D036022:Capsid Proteins; D016023:Integrins; D011991:Receptors, Virus; C442501:VP1 protein, Foot-and-mouth disease virus; C073878:integrin alphavbeta6