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Foot-and-Mouth Disease Virus Receptors: Comparison of Bovine _V Integrin Utilization by Type A and O Viruses

Foot-and-Mouth Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, New York 11944-0848

Received 22 July 2002/ Accepted 14 November 2002

Three members of the _V integrin family of cellular receptors, _Vß₁, _Vß₃, and _Vß₆, 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 ßG-ßH (G-H) loop of VP1. Other _V integrins, as well as several other integrins, recognize and bind to RGD motifs on their natural ligands and also may be candidate receptors for FMDV. To analyze the roles of the _V integrins from a susceptible species as viral receptors, we molecularly cloned the bovine ß₁, ß₅, and ß₆ integrin subunits. Using these subunits, along with previously cloned bovine _V and ß₃ subunits, in a transient expression assay system, we compared the efficiencies of infection mediated by _Vß₁, _Vß₃, _Vß₅, and _Vß₆ among three strains of FMDV serotype 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 _Vß₃ and _Vß₆ with relatively high efficiency, while only one virus utilized _Vß₁ with moderate efficiency. In contrast, both type O viruses utilized _Vß₆ and _Vß₁ with higher efficiency than _Vß₃. Only low levels of viral replication were detected in _Vß₅-expressing cells infected with either serotype. Experiments in which the ligand-binding domains among the ß subunits were exchanged indicated that this region of the integrin subunit appears to contribute to the differences in integrin utilizations 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.

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