Induction of Partial Protection against Foot and Mouth Disease Virus in Guinea Pigs by Neutralization with the Integrin β6-1 Subunit

The mechanism by which the foot-and-mouth disease virus (FMDV) initiates infection of cells is thought to involve the attachment of the viral capsid to host integrins on the surface of target cells. However, the role of integrins in FMDV infection still needs to be fully understood, although it has been demonstrated that integrin alpha v beta 6 interferes with FMDV in vitro and results in neutralization of its infectivity. In the present study, we describe the cloning and sequencing of suckling mouse integrin beta 6 and the subsequent expression of two segments of integrin beta 6 extracellular domains: beta 6-1 (which contains the ligand-binding domain) and beta 6-2. Sequencing of the mouse integrin beta 6 subunit revealed close homology (similar to 90%) with its human counterpart. When recombinant integrin extracellular domains beta 6-1 and beta 6-2 formulated with adjuvant were inoculated into guinea pigs, anti-integrin antibody expression was high before FMDV challenge. Interestingly, guinea pigs (50%) inoculated with integrin beta 6-1 were protected from FMDV infection; in contrast, none of the animals inoculated with integrin beta 6-2 were protected. This result indicates that an integrin blockade may be able to interfere with FMDV infection in vivo, which raises the possibility that targeting integrin in vivo may be the basis for a new strategy to control FMDV infection.