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Integrin expression in the upper respiratory tract of bovines, and the importance as receptors for FMDV infection

Background: FMDV has been reported to use a number of av integrins as receptors to initiate infection of cells in culture. However, the contribution of specific integrins to FMDV tropism and pathogenesis were unknown. Accordingly, the aim was to characterise integrin expression in the upper respiratory tract during infection with FMDV. In addition, stable cell lines expressing one of the known integrin receptors for FMDV were generated to facilitate the detailed analysis of the roles played by integrins and heparan sulphate during virus infection.

Results: A clear correlation was demonstrated between integrin expression and sites of FMDV replication. This work established integrin avb6 as the receptor most likely used by FMDV to target epithelial cells in the bovine hosts. Somewhat unexpected results were also obtained, showing that the role of heparan sulphate may not be confined to cell culture adaptation of virus. Heparan sulphate chains were found to be required for correct assembly of the integrin avb6. In addition, avb6 receptors lacking heparan sulphate chains showed a reduced specificity for RGD containing ligands typical of the cell binding receptor in the VP1 G-H loop of FMDV.

The studies have identified the importance of integrins, in particular integrin avb6, for FMDV infection. Moreover, it is now known that heparan sulphate chains provide essential requirements for correct integrin assembly at the surface of cells. This is of particular importance for vaccine manufacturers, due to the fact that cell culture passage of FMDV creates virus with high heparan sulphate binding capacity. These studies may be also prove useful for the design of antiviral substances specifically inhibiting virus binding to target epithelial cells.

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Reported by

INSTITUTE FOR ANIMAL HEALTH
Pirbright Laboratory, Ash Road
GU24 ONF Pirbright
United Kingdom
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