PERTURBATIONS IN THE SURFACE-STRUCTURE OF A22 IRAQ FOOT-AND-MOUTH-DISEASE VIRUS ACCOMPANYING COUPLED CHANGES IN HOST-CELL SPECIFICITY AND ANTIGENICITY

Background: Foot-and-mouth disease virus (FMDV) is an extremely infect ious and antigenically diverse picornavirus of cloven-hoofed an mals. Strains of the A22 subtype have been reported to change antigenically when adapted to different growth conditions. To investigate the struct ural basis of this phenomenon we have determined the structures of two variants of an A22 virus. Results: The structures of monolayer- and s uspension-cell-adapted A22 FMDV have been determined by X-ray crystall ography. Picornaviruses comprise four capsid proteins, VP1-4. The majo r antigenic loop of the cal,sid protein VP1 is flexible in both varian ts of the A22 subtype but its overall disposition is distinct from tha t observed in other FMDV serotypes (O and C). A detailed structural co mparison between A22 FMDV and a type O virus suggests that different c onformations in a portion of the major antigenic loop of VP1 (the GH l oop, which is also central to receptor attachment) result in distinct folds of the adjacent VP3 GH loop. Also, a single mutation (Glu82-->Gl y) on the surface of VP2 in the suspension-cell-adapted virus appears to perturb the structure of the VPI GH loop. Conclusions: The GH loop of VP1 is flexible in three serotypes of FMDV, suggesting that flexibi lity is important in both antigenic variability and structural communi cation with other regions of the virus capsid. Our results illustrate two instances of the propagation of structural perturbations across th e virion surface: the change in the VP3 GH loop caused by the VP1 GH l oop and the Glu82-->Gly change in VP2 which we believe perturbs the GH loop of VP1. In the latter case, the amplification of the sequence ch anges leads to differences, between the monolayer- and suspension-cell -adapted viruses, in host-cell interactions and antigenicity.