Location and Characterization of the Antigenic Portion of the FMDV Immunizing Protein

Abstract

SUMMARYPurified foot-and-mouth disease virus (FMDV) of type OIK was treated with several endopeptidases of differing specificity. The immunizing protein VPTh r was cleaved into two detectable fragments by all enzymes except for glutamic acid-specific Staphylococcus aureus V8 protease. The longest fragments were generated by mouse submaxillary gland protease and the shortest by trypsin treatment of the intact virion. Several fragments, including the peptides resulting from the cyanogen bromide (CNBr) cleavage of the isolated protein VPTh r, were characterized in terms of their molecular weights, N-and C-terminal amino acids, and ability to induce virus-specific antibodies. The order of the fragments along the protein was determined, and then located on the amino acid sequence of the protein. Two enzyme-sensitive areas of the protein were found on the surface of the virion: between sequence positions 138 and 154 and between portion 200 and the C terminus. Peptides containing these sections were able to induce neutralizing antibodies against the homologous FMDV. When the virus was treated with trypsin or with chymotrypsin, several amino acids between the detectable fragments were lost and the infectivity of the virus was reduced. The infectivity was retained, however, when the enzyme treatment resulted in cleavage of protein with no loss of amino acids or only the cutting away of the C-terminal section. These results suggest that the property of cell attachment is restricted to small regions of the surface of the virus particle.

Evidence of partial protection against foot-and-mouth disease in cattle immunized with a recombinant adenovirus vector expressing the precursor polypeptide (P1) of foot-and-mouth disease virus capsid proteins.

“…For this study we cloned into an adenovirus vector the gene which expresses the precursor polyprotein of the four capsid proteins (P1) of FMDV. This polyprotein was chosen as it has been shown to contain most of the continuous and discontinuous B cell epitopes involved in the induction of neutralizing antibodies to FMDV (Bittle et al, 1982 ;Strohmaier et al, 1982 ;Saiz et al, 1994 ;Abrams et al, 1995 ;Brown, 1995 ;Mateu, 1995), as well as T-cell epitopes recognized by cattle and swine (Collen, 1994 ;Rodriguez et al, 1994 ;van Lierop et al, 1995). The conformation of the expressed products of this gene cloned into baculovirus and vaccinia vectors has been shown to be antigenically similar to native capsid proteins (Saiz et al, 1994 ;Sanz-Parra et al, 1998).…”

Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C1-Barcelona

“…bodies recognize FMDV GH loop (residues 136-150 of capsid protein VP1 [2]), which includes several overlapping linear epitopes [3] and is also termed antigenic site A. Site A includes highly conserved residues, such as an Arg-Gly-Asp (RGD) motif, and two leucines ( 144 Leu, 147 Leu), which are deeply involved in cell and antibody recognition events [4].…”

Evolution subverting essentiality: Dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus

“…First, the FMDV structures determined by Stuart and colleagues (16)(17)(18)(19) revealed that, contrary to other picornaviruses, no canyon or pit was present on the smooth FMDV surface. Furthermore, the critical receptor recognition Arg-Gly-Asp domain was located on a highly mobile loop (the G-H loop of VP1), which was also a major antigenic site for the virus (20)(21)(22). Additional structural work by Fita and colleagues (23) further indicated that the ArgGly-Asp motif is not only part of the receptor recognition site but it also interacts directly with some anti-viral neutralizing antibodies.…”