Submitted to: American Society of Cell Biology Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 7/30/2002
Publication Date: N/A
Technical Abstract: Three members of the alphaV integrin family, alphaVbeta1, alphaVbeta3, and alphaVbeta6 have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. The virus interacts with these receptors via a highly conserved arginine-glycine-aspartic acid (RGD) amino acid sequence motif located within the betaG-betaH (G-H) loop of VP1. Other alphaV integrins may be candidate receptors for FMDV. To analyze the roles of the alphaV integrins from a susceptible species as viral receptors, we molecularly cloned the bovine beta1, beta5 and beta6 integrin subunits. Using these subunits, along with previously cloned bovine alphaV and beta3 subunits, in a transient expression assay system, we compared the efficiency of infection mediated by alphaVbeta1, alphaVbeta3, alphaVbeta5, and alphaVbeta6 between three strains of FMDV serotypes A and two strains of serotype O. While all the viruses could infect cells expressing these integrins, they exhibited different efficiencies of integrin utilization. All the type A viruses used alphaVbeta3 and alphaVbeta6 with relatively high efficiency, while only one utilized alphaVbeta1 with moderate efficiency. In contrast, both type O viruses utilized alphaVbeta6 and alphaVbeta1 with higher efficiency than alphaVbeta3. Only low levels of viral replication were detected in alphaVbeta5-expressing cells infected with either serotype. Experiments, in which the ligand-binding domains among the beta subunits were exchanged, indicated that this region of the integrin subunit appears to play a role in differences in integrin utilization among strains. In contrast, the G-H loops of the different viruses do not appear to be involved in this phenomenon. Thus the ability of the virus to utilize multiple integrins in vitro may be a reflection of the use of multiple receptors during the course of infection within the susceptible host.