Revertants of poliovirus escape mutants: new insights into antigenic structures.
Poliovirus variants that escape neutralization by monoclonal antibodies (mAbs) have previously been selected and characterized in order to determine antigenic sites on the surface of the virion. Phenotypic revertants of poliovirus type 1 escape mutants were selected within all three antigenic sites (sites 1, 2, and 3) on the basis of their reactivity with the selecting mAb. The phenotypic and genotypic properties of these revertants were determined by binding and neutralization assays. Sequencing of the viral RNA revealed different types of reversions. Besides reversion to wild-type genotype, we found phenotypic revertants which had amino acid substitutions differing from wild type, thus revealing amino acids that are also tolerated by the antibody. In another type of revertant, alterations in other parts of the epitope were found, providing a refined resolution of a particular antibody recognition site. Most of the revertants regained the property to be neutralized by the mAb. However, in one case they remained resistant to neutralization despite the fact that binding to the selecting antibody was reestablished. These results indicate that virus neutralization might be achieved by different mechanisms depending on the particular mAb.
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Germany.
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D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000956:Antigens, Viral / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D007525:Isoelectric Focusing; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D017955:Poliovirus / Q000235:genetics* / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D012367:RNA, Viral