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 infectious and antigenically diverse picornavirus of cloven-hoofed animals. Strains of the A22 subtype have been reported to change antigenically when adapted to different growth conditions. To investigate the structural basis of this phenomenon we have determined the structures of two variants of an A22 virus.


RESULTS
The structures of monolayer- and suspension-cell-adapted A22 FMDV have been determined by X-ray crystallography. Picornaviruses comprise four capsid proteins, VP1-4. The major antigenic loop of the capsid protein VP1 is flexible in both variants of the A22 subtype but its overall disposition is distinct from that observed in other FMDV serotypes (O and C). A detailed structural comparison between A22 FMDV and a type O virus suggests that different conformations in a portion of the major antigenic loop of VP1 (the GH loop, which is also central to receptor attachment) result in distinct folds of the adjacent VP3 GH loop. Also, a single mutation (Glu82-->Gly) on the surface of VP2 in the suspension-cell-adapted virus appears to perturb the structure of the VP1 GH loop.


CONCLUSIONS
The GH loop of VP1 is flexible in three serotypes of FMDV, suggesting that flexibility is important in both antigenic variability and structural communication with other regions of the virus capsid. Our results illustrate two instances of the propagation of structural perturbations across the virion surface: the change in the VP3 GH loop caused by the VP1 GH loop 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 changes leads to differences, between the monolayer- and suspension-cell-adapted viruses, in host-cell interactions and antigenicity.
Curry
S
S
Pirbright Laboratory, Institute for Animal Health, Pirbright, Surrey, GU24 0NF, UK.
Fry
E
E
Blakemore
W
W
Abu-Ghazaleh
R
R
Jackson
T
T
King
A
A
Lea
S
S
Newman
J
J
Rowlands
D
D
Stuart
D
D
D000956:Antigens, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000737:chemistry* / Q000276:immunology; D002213:Capsid / Q000737:chemistry* / Q000235:genetics; D002648:Child; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D014961:X-Ray Diffraction
D000956:Antigens, Viral