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Journal of Virology, September 2004, p. 9773-9781, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9773-9781.2004

Interactions of Foot-and-Mouth Disease Virus with Soluble Bovine _Vß₃ and _Vß₆ Integrins

Hernando Duque,^, Michael LaRocco, William T. Golde, and Barry Baxt^*

Foot-and-Mouth Disease Research Unit, Plum Island Animal Disease Center, USDA Agricultural Research Service, Greenport, New York

Received 8 January 2004/ Accepted 16 May 2004

At least four members of the integrin family of receptors, _Vß₁, _Vß₃, _Vß₆, and _Vß₈, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. Our investigators have recently shown that the efficiency of receptor usage appears to be related to the viral serotype and may be influenced by structural differences on the viral surface (H. Duque and B. Baxt, J. Virol. 77:2500-2511, 2003). To further examine these differences, we generated soluble _Vß₃ and _Vß₆ integrins. cDNA plasmids encoding the individual complete integrin _V, ß₃, and ß₆ subunits were used to amplify sequences encoding the subunits' signal peptide and ectodomain, resulting in subunits lacking transmembrane and cytoplasmic domains. COS-1 cells were transfected with plasmids encoding the soluble _V subunit and either the soluble ß₃ or ß₆ subunit and labeled with [³⁵S]methionine-cysteine. Complete subunit heterodimeric integrins were secreted into the medium, as determined by radioimmunoprecipitation with specific monoclonal and polyclonal antibodies. For the examination of the integrins' biological activities, stable cell lines producing the soluble integrins were generated in HEK 293A cells. In the presence of divalent cations, soluble _Vß₆ bound to representatives of type A or O viruses, immobilized on plastic dishes, and significantly inhibited viral replication, as determined by plaque reduction assays. In contrast, soluble _Vß₃ was unable to bind to immobilized virus of either serotype; however, virus bound to the immobilized integrin, suggesting that FMDV binding to _Vß₃ is a low-affinity interaction. In addition, soluble _Vß₃ did not neutralize virus infectivity. Incubation of soluble _Vß₆ with labeled type A₁₂ or O₁ resulted in a significant inhibition of virus adsorption to BHK cells, while soluble _Vß₃ caused a low (20 to 30%), but consistent, inhibition of virus adsorption. Virus incubated with soluble _Vß₆ had a lower sedimentation rate than native virus on sucrose density gradients, but the particles retained all of their structural proteins and still contained bound integrin and, therefore, were not exhibiting characteristics of a picornavirus A particle.

Present address: USDA Animal Plant Health Inspection Service, Veterinary Services, Foreign Animal Disease Diagnostic Laboratory, Greenport, NY 11944.

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