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J Gen Virol 70 (1989), 45-57; DOI 10.1099/0022-1317-70-1-45
© 1989 Society for General Microbiology

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Host Cell Selection of Antigenic Variants of Foot-and-Mouth Disease Virus

C. Bolwell1, A. L. Brown1, P. V. Barnett1, R. O. Campbell1, B. E. Clarke1, N. R. Parry1, E. J. Ouldridge2, F. Brown1 and D. J. Rowlands1

1 Wellcome Biotechnology Limited, Langley Court, Beckenham, Kent BR3 3BS
and2 Coopers Animal Health Limited, Ash Road, Pirbright, Woking, Surrey GU24 0NQ, U.K.

Foot-and-mouth disease virus (FMDV) A22 Iraq 24/64 adapted to grow in BHK monolayer cells induced antibodies which neutralized many isolates belonging to the A serotype. Plaque-purified virus isolated from this stock also induced broadly reactive antibodies, showing that this property is not due to the combined response to a mixture of variants in the original stock virus. However, viruses obtained by passage in suspension BHK cells of either the monolayer cell-adapted virus or a virus cloned from this stock resulted in the selection of virus which induced antibodies with highly specific neutralizing activity. In addition to their antigenic properties the monolayer and suspension cell-adapted viruses could be distinguished by plaque morphology, tendency to aggregate and ability to attach to BHK cells. Monoclonal antibodies (MAbs) induced with the plaque-purified monolayer-adapted virus had neutralizing activity almost as broad as polyclonal serum, showing that this property can be represented by a single epitope on the virus. These neutralizing MAbs recognize a trypsin-sensitive epitope on the virus. Surprisingly, sequence analysis of the structural protein-coding regions of the genomic RNAs of monolayer and suspension cell-adapted viruses showed no amino acid differences in VP1, the protein known to contain the major neutralization epitope in FMDV and to be the only protein susceptible to cleavage by trypsin in the virus particle. Although three coding differences were found in the capsid protein these were all located in VP2.

Keywords: FMDV, capsid protein, cell selection

Received 20 June 1988; accepted 10 October 1988.


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