Structure of a major immunogenic site on foot-and-mouth disease virus

Abstract

Attachment of foot-and-mouth disease virus (FMDV) to its cellular receptor involves a long and highly antigenic loop containing the conserved sequence, Arg-Gly-Asp, a motif known to be a recognition element in many integrin-dependent cell adhesion processes. In our original crystal structure of FMDV the Arg-Gly-Asp-containing loop ('the loop'), located between beta-strands G and H of capsid protein VP1, was disordered and hence essentially invisible. We previously surmised that its disorder is enhanced by a disulphide bond linking the base of the loop (Cys 134) to Cys 130 of VP2 (ref. 8). We report here the crystal structure of the virus in which this disulphide is reduced. Reduced virus retains infectivity and serological experiments suggest that some of the loop's internal structure is conserved. But here its structure has become sufficiently ordered to allow us to describe an unambiguous conformation, which we relate to some key biological properties of the virus.

Liposomes enhance delivery and expression of an RGD-oligolysine gene transfer vector in human tracheal cells

“…Integrins are natural targets for receptormediated cell entry used by a variety of pathogenic micro-organisms, including bacteria 14 and viruses. 15,16 In particular, the adenovirus, a candidate for viral gene therapy, has been shown to require RGD-binding of integrins for internalisation. 17 While both cationic liposome and receptor-mediated molecular conjugates suffer from relatively low transfection efficiencies the association of the two can substantially increase transfection as demonstrated in lung endothelial cells when a poly-l-lysine anti-thrombomodulin antibody conjugate and DNA where associated with a cationic liposome.…”

Evaluation of Genetically Engineered Derivatives of a Chinese Strain of Foot-and-Mouth Disease Virus Reveals a Novel Cell-Binding Site Which Functions in Cell Culture and in Animals

“…These studies indicate that naturally occurring isolates of the virus appear to bind to cells via a highly conserved (46), surface-exposed arginine-glycine-aspartic acid (RGD)-containing loop in capsid protein 1D (37). Further, a variety of approaches have indicated that this loop interacts with one or more of the RGD-binding integrins, including integrins ␣v␤3 (44), ␣v␤6 (28), and ␣v␤1 (27).…”

A second RGD motif in the 1D capsid protein of a SAT1 type foot-and-mouth disease virus field isolate is not essential for attachment to target cells

“…1A). Based on the openUP (July 2007) previously elucidated crystal structure of the type O 1 BFS virion (Logan et al, 1993), the KAP sequence is located on a short surface-exposed loop between βF and βG (Fig. 1B).…”

“…The capsid protein 1D contains a mobile loop between the βG and βH strands on the virus surface that not only contains the major immunodominant epitopes of the virion, but also a highly conserved arginine-glycine-aspartic acid (RGD) sequence (Acharya et al, 1989, Logan et al, 1993and Mateu, 1995.…”