Antibody and host cell recognition of foot-and-mouth disease virus (serotype C) cleaved at the Arg-Gly-Asp (RGD) motif: a structural interpretation.
Foot-and-mouth disease virus (FMDV) of serotype C (isolate C-S8c1) was cleaved in situ by trypsin at the Arg-Gly-Asp (RGD) motif, which is involved both in attachment of FMDV to cells and in recognition of a major antigenic site (site A) by antibodies. Though 99.4% of the RGD moieties were cleaved, the virus remained infectious. A synthetic peptide which represented the sequence of the VP1 G-H loop of C-S8c1, including the RGD motif, greatly inhibited FMDV attachment to cells. The same peptide inhibited, very effectively and to the same extent (50% inhibition at about 1 microM), the infectivity of both intact and trypsin-treated virus. Replacement of Asp with Glu at the RGD motif abolished the inhibitory effects of the peptide. Thus, the RGD motif is involved in the infectivity of both intact and RGD-cleaved serotype C FMDV. Trypsin treatment did not affect the reactivity of the virus with some monoclonal antibodies (MAbs) directed to site A whose epitopes involve mainly residues contiguous to the cleaved bond, but diminished the reactivity with site A MAbs whose epitopes include the RGD sequence and flanking residues. However, high concentrations of any site A MAb tested neutralized close to 100% of the infectious trypsin-treated virus. We propose that, in spite of covalent cleavage, the high number of intramolecular non-covalent interactions observed within the G-H loop of FMDV C-S8c1 (complexed to antibody) may hold the RGD in a nearly correct conformation and allow--albeit with reduced affinity--antibody and cell receptor recognition of RGD-cleaved FMDV.
Hernández
J
J
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, Spain.
Valero
M L
ML
Andreu
D
D
Domingo
E
E
Mateu
M G
MG
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000276:immunology*; D000939:Epitopes; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000502:physiology*; D013329:Structure-Activity Relationship; D014357:Trypsin
D000914:Antibodies, Viral; D000939:Epitopes; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D014357:Trypsin