title: Crystal structure of Swine vesicular disease virus and implications for host adaptation.
abstract: Swine vesicular disease virus (SVDV) is an Enterovirus of the family Picornaviridae that causes symptoms indistinguishable from those of foot-and-mouth disease virus. Phylogenetic studies suggest that it is a recently evolved genetic sublineage of the important human pathogen coxsackievirus B5 (CBV5), and in agreement with this, it has been shown to utilize the coxsackie and adenovirus receptor (CAR) for cell entry. The 3.0-A crystal structure of strain UK/27/72 SVDV (highly virulent) reveals the expected similarity in core structure to those of other picornaviruses, showing most similarity to the closest available structure to CBV5, that of coxsackievirus B3 (CBV3). Features that help to cement together and rigidify the protein subunits are extended in this virus, perhaps explaining its extreme tolerance of environmental factors. Using the large number of capsid sequences available for both SVDV and CBV5, we have mapped the amino acid substitutions that may have occurred during the supposed adaptation of SVDV to a new host onto the structure of SVDV and a model of the SVDV/CAR complex generated by reference to the cryo-electron microscopy-visualized complex of CBV3 and CAR. The changes fall into three clusters as follows: one lines the fivefold pore, a second maps to the CAR-binding site and partially overlaps the site for decay accelerating factor (DAF) to bind to echovirus 7 (ECHO7), and the third lies close to the fivefold axis, where the low-density lipoprotein receptor binds to the minor group of rhinoviruses. Later changes in SVDV (post-1971) map to the first two clusters and may, by optimizing recognition of a pig CAR and/or DAF homologue, have improved the adaptation of the virus to pigs.
authors.affiliation: Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, United Kingdom.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Fry
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Knowles
authors.forename: John W I
authors.initials: JW
authors.lastname: Newman
authors.forename: Ginette
authors.initials: G
authors.lastname: Wilsden
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
authors.forename: Andrew M Q
authors.initials: AM
authors.lastname: King
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D029822:Enterovirus B, Human / Q000737:chemistry / Q000472:pathogenicity / Q000648:ultrastructure; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism; D013552:Swine; D013555:Swine Vesicular Disease / Q000821:virology
chemical_list: C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus