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

SummaryFoot-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 αVβ1, αVβ3, αVβ6, and αVβ8 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, αVβ3 and αVβ6, within epithelial tissues from FMDV-infected and uninfected cattle in order to understand the role of these receptors in tissue tropism. Integrin αVβ6 was expressed by epithelial cells in tissues that are important sites for FMDV replication (i.e. tongue and coronary band). Integrin αVβ3 was detected in epithelium of all tissues examined except tongue. In addition, αVβ3 expression was associated with blood vessels in all tissues examined. In infected tissues, αVβ6 integrin was distributed on the surface of those epithelial cells also expressing FMDV antigen. Although integrin αVβ3 has been shown to be a receptor for FMDV, no expression of αVβ3 was associated with FMDV-positive keratinocytes in the tongue. In contrast, podal epithelial cells containing FMDV antigen also expressed αVβ3 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.