Point mutations in glycoprotein gene of vesicular stomatitis virus (New Jersey serotype) selected by resistance to neutralization by epitope-specific monoclonal antibodies.
Antigenic variants of the New Jersey serotype of vesicular stomatitis virus (VSV-NJ) were isolated and cloned by selecting virus plaques resistant to neutralization by high-titered monoclonal antibodies (MAbs) directed to glycoprotein (G) epitopes V, VI, VII, or VIII. The G proteins of each neutralization-resistant virus variant also exhibited markedly reduced antigenic reactivity with each corresponding epitope-specific MAb as determined by enzyme-linked immuno-absorbent assay and by Western blot analysis. Loss of antigenic reactivity of certain mutant G proteins to a MAb other than the one used to select the mutant virus suggested close antigenic proximity, particularly for epitopes VI and VII. The virion RNAs coding for the entire G gene of the wild-type virus and 10 MAb-induced mutants were sequenced by primer DNA extension using the dideoxy method. Each mutant G gene exhibited only a single nucleotide change, leading in each case to a single amino acid substitution, as follows: Glu210----Lys for all three mutants selected by MAb14 (epitope VII); Pro268----Thr for one mutant selected by MAb12 (epitope VI); Ser277----Lys for all three mutants selected by MAb15 (epitope VIII); and Glu364----Lys for all three mutants selected by MAb11 (epitope V). These neutralizing MAb-selected mutations are clustered in the middle third of the 517-amino acid VSV-NJ G protein, presumably resulting in conformational changes that alter recognition of one or more antigenic determinants by a specific monoclonal antibody.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009154:Mutation; D018116:Vesiculovirus / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; C028391:G protein, vesicular stomatitis virus; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins