Analysis of Foot-and-Mouth Disease Virus Integrin Receptor Expression in Tissues from Naive and Infected Cattle

Summary Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals principally affecting cattle, pigs and sheep. FMD virus (FMDV) uses the α V β 1 , α V β 3 , α V β 6 , and α V β 8 integrins as receptors in vitro via a highly conserved arginine–glycine–aspartic acid amino acid sequence motif located within the βG-βH loop of VP1. Immunofluorescence and confocal microscopy were used to study the expression of two major FMDV receptors, α V β 3 and α V β 6 , within epithelial tissues from FMDV-infected and uninfected cattle in order to understand the role of these receptors in tissue tropism. Integrin α V β 6 was expressed by epithelial cells in tissues that are important sites for FMDV replication (i.e. tongue and coronary band). Integrin α V β 3 was detected in epithelium of all tissues examined except tongue. In addition, α V β 3 expression was associated with blood vessels in all tissues examined. In infected tissues, α V β 6 integrin was distributed on the surface of those epithelial cells also expressing FMDV antigen. Although integrin α V β 3 has been shown to be a receptor for FMDV, no expression of α V β 3 was associated with FMDV-positive keratinocytes in the tongue. In contrast, podal epithelial cells containing FMDV antigen also expressed α V β 3 integrin. Thus, at the cellular level the expression of these two integrins correlates with susceptibility to infection and may contribute substantially to viral tropism in FMD pathogenesis.