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Title: Structure of Foot-and-mouth Disease virus serotype A1061 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation

Author
item FRY, ELIZABETH
item NEWMAN, JOHN
item CURRY, STEPHEN
item NAJJAM, SALOUA
item JACKSON, TERRY
item BLAKEMORE, WENDY
item LEA, SUSAN
item Miller, Laura
item BURMAN, ALISON
item KING, ANDREW
item STUART, DAVID

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/25/2005
Publication Date: 7/1/2005
Citation: Fry, E.E., Newman, J.W.I., Curry, S., Najjam, S., Jackson, T., Blakemore, W., Lea, S.M., Miller, L., Burman, A., King, A.M.Q., Stuart, D.I. 2005. Structure of Foot-and-mouth Disease virus serotype A1061 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation. Journal of General Virology. 86:1909-1920.

Interpretive Summary: Foot-and-mouth Disease viruses (FMDVs) are highly contagious, infecting cloven-hoofed animals, and outbreaks of disease have great economic importance. Control and eradication of the virus through vaccination and/or slaughter have not proven satisfactory and a more rigorous understanding of the basis of antigenic variation and receptor utilization may lead to improved vaccines or novel methods of control. Heparan sulfate has an important role in cell entry by Foot-and-mouth Disease virus (FMDV). The structure of FMDV A1061 (a cell culture-adapted strain) complexed with heparin has now been determined.

Technical Abstract: Foot-and-mouth Disease viruses (FMDVs) target epithelial cells via integrin receptors, but can acquire the capacity to bind cell-surface heparan sulphate (or alternative receptors) on passage in cell culture. Vaccine viruses must be propagated in cell culture and, hence, some rationale for the selection of variants in this process is important. Crystal structures are available for type O, A and C viruses and also for a complex of type O strain O1BFS with heparin. The structure of FMDV A1061 (a cell culture-adapted strain) complexed with heparin has now been determined. This virus has an RGSD motif in place of the otherwise conserved RGD integrin-binding motif and the potential to bind heparan sulphate (suggested by sequence analyses). FMDV A1061 was closely similar in structure to other serotypes, deviating most in antigenic sites. The VP1 GH loop comprising the integrin-binding motif was disordered. Heparin bound at a similar site and in a similar conformation to that seen in the analogous complex with O1BFS, although the binding had a lower affinity and was more ionic. Atomic coordinates have been deposited in the Protein Data Bank under accession codes 1ZBE and 1ZBA.