Prediction and characterization of novel epitopes of serotype A foot-and-mouth disease viruses circulating in East Africa using site-directed mutagenesis

Bari, F. D., Parida, S., Asfor, A. S., Haydon, D. T. , Reeve, R. , Paton, D. J. and Mahapatra, M. (2015) Prediction and characterization of novel epitopes of serotype A foot-and-mouth disease viruses circulating in East Africa using site-directed mutagenesis. Journal of General Virology, 96, pp. 1033-1041. (doi: 10.1099/vir.0.000051) (PMID:25614587) (PMCID:PMC4631058)

Abstract

Epitopes on the surface of the foot-and-mouth disease virus (FMDV) capsid have been identified by monoclonal antibody (mAb) escape mutant studies leading to the designation of four antigenic sites in serotype A FMDV. Previous work focused on viruses isolated mainly from Asia, Europe and Latin America. In this study we report on the prediction of epitopes in African serotype A FMDVs and testing of selected epitopes using reverse genetics. Twenty-four capsid amino acid residues were predicted to be of antigenic significance by analysing the capsid sequences (n = 56) using in silico methods, and six residues by correlating capsid sequence with serum–virus neutralization data. The predicted residues were distributed on the surface-exposed capsid regions, VP1–VP3. The significance of residue changes at eight of the predicted epitopes was tested by site-directed mutagenesis using a cDNA clone resulting in the generation of 12 mutant viruses involving seven sites. The effect of the amino acid substitutions on the antigenic nature of the virus was assessed by virus neutralization (VN) test. 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Haydon, Professor Daniel and Reeve, Professor Richard and Parida, Professor Satya and Mahapatra, Dr Madhuchhanda and Paton, Professor David
• Authors: Bari, F. D., Parida, S., Asfor, A. S., Haydon, D. T., Reeve, R., Paton, D. J., and Mahapatra, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Journal of General Virology
• Publisher: Society for General Microbiology
• ISSN: 0022-1317
• ISSN (Online): 1465-2099
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Journal of General Virology 96:1033-1041
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
50716	1	Improving the quality of FMD (Foot-and-mouth disease) vaccines by understanding the correlation of vaccine-induced protection with humoral and cellular immune responses	Richard Reeve	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/H009175/1	RI BIODIVERSITY ANIMAL HEALTH & COMPMED