|O'Donnell, Vivian - UNIV OF CONNECTICUT|
|Gregg, Douglas - FORMER USDA ARS NAA PIADC|
|Baxt, Barry - FORMER USDA ARS NAA PIADC|
Submitted to: Journal of Comparative Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 22, 2009
Publication Date: N/A
Interpretive Summary: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals principally affecting cattle, pigs and sheep. The disease is caused by the foot-and-mouth disease virus (FMDV) and results in large economic losses to countries where it occurs. In order for the virus to cause disease, FMDV must first infect cells of susceptible species by binding to specific molecules on the cell surface, called receptors. We have previously identified the specific receptors for FMDV as members of a large family of membrane proteins called integrins. The two major FMDV receptors are the alphaV/beta3 (aVb3) and the alphaV/beta6 (aVb6) integrins. Integrins are important receptors and play a role in how cells interact with each other and with their environment in an organism. We have now expanded on our previous studies and found that the integrin aVb6 serves as the major receptor that determines virus tropism in cattle. As for aVb3 its distribution suggests that could play a role as a secondary receptor helping the virus to spread to secondary sites of infection. These results will be useful for understanding virus distribution and tropism and in designing countermeasures to prevent or limit FMDV infection.
Technical Abstract: 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 alphaVbeta1, alphaVbeta3, alphaVbeta6 and alphaVbeta8 integrins as receptors in vitro via a highly conserved arginine-glycine-aspartic acid amino acid sequence motif located within the betaG-betaH loop of VP1. Immunofluorescence and confocal microscopy were used to study the expression of two major FMDV-receptors, alphaVbeta3 and alphaVbeta6, within epithelial tissues from FMDV-infected and uninfected cattle to understand the role of these receptors in tissue tropism. In normal tissues alphaVbeta6 was found in epithelial cells in tissues that are important sites for FMDV replication (i.e. tongue and coronary band). Integrin alphaVbeta3 was detected in epithelial cell layers and blood vessels of all the tissues examined, except tongue. In infected tissues, alphaVbeta6 integrin was distributed on the surface of the epithelial cells also expressing FMDV antigen. Although integrin alphaVbeta3 has been shown to be a receptor for FMDV, no expression of alphaVbeta3 was associated with FMDV-positive keratinocytes in tongue. In contrast podal epithelial cells containing FMDV-antigen also expressed alphaVbeta3 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.