Natural feline leukemia virus variant escapes neutralization by a monoclonal antibody via an amino acid change outside the antibody-binding epitope.
We have molecularly cloned a natural variant of feline leukemia virus subtype B. This isolate is unique in that it is not neutralized by a monoclonal antibody which neutralized all other feline leukemia virus isolates tested, including members of the A, B, and C subtypes. Western immunoblotting indicated that the monoclonal antibody was less able to bind to the gp70 of the resistant isolate (designated lambda B1) than to the gp70s of susceptible viruses. Nucleotide sequence analysis of the envelope gene of lambda B1 revealed a high degree of homology with the susceptible Snyder-Theilen, Gardner-Arnstein, and Rickard subtype B isolates, including the presence of a 5-amino-acid minimal binding epitope required for binding by the neutralizing monoclonal antibody. The only change within the vicinity of this epitope was in a single nucleotide, and this difference changed a proline residue to leucine three amino acids from the N terminus of the binding epitope. Competitive binding studies with synthetic peptides indicated that substitution of leucine for proline resulted in a 10-fold decrease in the ability of the peptide to compete for antibody binding to native antigen. The results are consistent with the interpretation that this amino acid change lowers the affinity of antibody binding, resulting in failure of the antibody to neutralize the variant virus.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D005796:Genes; D005814:Genes, Viral; D014644:Genetic Variation; D005256:Leukemia Virus, Feline / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins