Prediction and characterization of novel epitopes of serotype A foot-and-mouth disease viruses circulating in East Africa using site-directed mutagenesis.
Bottom Line: Mutations at four different positions, namely VP1-43, VP1-45, VP2-191 and VP3-132, led to significant reduction in VN titre (P value = 0.05, 0.05, 0.001 and 0.05, respectively).This is the first time, to our knowledge, that the antigenic regions encompassing amino acids VP1-43 to -45 (equivalent to antigenic site 3 in serotype O), VP2-191 and VP3-132 have been predicted as epitopes and evaluated serologically for serotype A FMDVs.This identifies novel capsid epitopes of recently circulating serotype A FMDVs in East Africa.
Affiliation: The Pirbright Institute, Ash Road, Woking, Surrey, GU24 0NF, UK.Show MeSH
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Mentions: The highest antigenicity score in ConSurf was 5.29 and the top scoring 33 amino acid positions were compared with the entropy prediction results. Out of these, 24 were selected by both methods showing good agreement (86 %) between the two prediction methods (Fig. 1). All the 24 predicted residues were located on the outer surface of the virus capsid (Fig. 2b) except two residues, VP2-207 and VP3-35, which were internal (Fig. 2c). Eleven, eight and five predicted residues are present in VP1, VP2 and VP3, respectively (Table 1). Out of these, seven (29.2 %) have been previously reported in serotype A viruses; VP1-139/141/142, -149 (Thomas et al., 1988), VP1-198 (Saiz et al., 1991), VP3-70 (Thomas et al., 1988) and VP2-134 were reported to be of antigenic significance in serotype A viruses previously (Saiz et al., 1991) or to influence mAb binding in serotype O (Mahapatra et al., 2008). Previously, in silico epitope predictions performed using the A1061 crystal structure identified six (VP1-196/197/198, VP2-191 and VP3-70/71) of the 24 residues (Borley et al., 2013). Because ConSurf predicts epitopes with reference to the 3D structure and also by comparing evolutionary conservation rates of the aligned amino acid sequences, it is expected that it might provide more specific predictions of epitopes than would entropy analysis. Accordingly, ConSurf selected VP1-148 (data not shown), a neutralizing conformational epitope reported earlier for serotype A (Mahapatra et al., 2011).
Affiliation: The Pirbright Institute, Ash Road, Woking, Surrey, GU24 0NF, UK.