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Updated: Mar 2, 2026
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus
Abhay Kotecha1, Quan Wang2, Xianchi Dong3,4
1Division of Structural Biology, The Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK.
Abstract:
Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections. HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding. Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy. In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues. In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
Insights
Foot-and-mouth disease virus (FMDV) uses an RGD motif to bind integrin receptors for cell entry. Tissue-culture adapted strains also interact with heparin sulfate, revealing new binding mechanisms.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Foot-and-mouth disease virus (FMDV) typically enters cells by binding integrin receptors, specifically αvβ6, through an arginine-glycine-aspartic acid (RGD) motif on capsid protein VP1.
- Tissue culture-adapted FMDV strains can infect cells independently of integrins by interacting with heparin sulfate (HS), a mechanism associated with viral attenuation in natural infections.
Purpose of the Study:
- To elucidate the high-resolution structural interactions between αvβ6 integrin and two tissue culture-adapted FMDV strains.
- To investigate the binding mechanisms of FMDV, including the role of the RGD motif and potential interactions with N-linked sugars.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was employed to determine the structures of αvβ6 integrin bound to tissue culture-adapted FMDV strains.
- Analysis of high-resolution structures to identify specific molecular interactions between viral proteins and the integrin receptor.
Main Results:
- The study visualized the fully open conformation of the αvβ6 integrin engaging with an extended GH loop of FMDV.
- Binding involved interactions with the conserved RGD motif and adjacent hydrophobic residues on the viral capsid.
- An N-linked glycan of the integrin was observed to bind at a previously identified heparin sulfate (HS) binding site on the virus, suggesting a functional role.
Conclusions:
- The findings reveal a dual binding mode for tissue culture-adapted FMDV, involving both integrin and HS-binding sites.
- The structural data provides new insights into FMDV cell entry mechanisms and the potential functional significance of integrin glycosylation in viral interactions.
