ABSTRACT
One of the major obstacles to the design of effective antiviral vaccines is the frequent generation of antigenic viral variants in the field. The types of variants that will become dominant during disease outbreaks is often unpredictable. However, here we report the genetic and antigenic characterization of emerging foot-and-mouth disease virus (FMDV) variants with antigenically critical amino acid substitutions predicted by model studies using reference viruses and monoclonal antibodies. The new variants belong to serotype C and have caused a number of recent disease outbreaks in Argentina. The variants harbor antigenically drastic amino acid substitutions in each of the antigenic sites identified in FMDV. In particular, a substitution found at a major antigenic site (site A, the G-H loop of VP1) had been repeatedly selected in viruses resistant to neutralization by monoclonal and polyclonal antibodies. The association of critical amino acid replacements at predicted positions with new FMD outbreaks has a number of implications for FMD epidemiology and for the design of vaccines intended to control diseases caused by highly variable RNA viruses.
Subject(s)
Antigens, Viral/genetics , Antigens, Viral/immunology , Aphthovirus/genetics , Aphthovirus/immunology , Amino Acid Sequence , Animals , Antibodies, Monoclonal , Cattle , Genome, Viral , Molecular Sequence Data , Sequence Homology, Amino Acid , Structure-Activity Relationship , Viral Vaccines/genetics , Viral Vaccines/immunologyABSTRACT
The PVX coat protein (CP) is involved in many aspects of plant-virus interaction (virion morphology, plant symptoms, viral pathogenesis and virulence, and genomic RNA accumulation). Different virus strains have been distinguished according to their compatibility with the host resistance genes Nx, Nb, and Rx. Substitution of the Thr 122 on the CP with a Lys in PVX strain HB has been shown to affect the response of potato cultivars with the Rx resistance gene. In PVX DX the avirulence determinant for the Nx gene has been localized in the Gln 78 of the coat. PVX strain MS, like PVX HB, is able to overcome the Rx, Nx, and Nb genes. Sequencing of the CP gene of PVX MS (EMBL accession number Z34261) shows that it has a Thr in codon 122 and a Gln in codon 78. These results suggest that, in addition to the coat protein gene, other regions of the viral genome are involved in the pathogenicity.
