Characterization of two antigenic sites recognized by neutralizing monoclonal antibodies directed against the fusion glycoprotein of human respiratory syncytial virus.
Two antigenic sites recognized by neutralizing monoclonal antibodies (MAbs) directed against the fusion (F) glycoprotein of human respiratory syncytial virus were mapped on the primary structure of the protein by (i) the identification of amino acid substitutions selected in antibody-escape mutants and (ii) the reactivity of synthetic peptides with MAbs. The first site contained several overlapping epitopes which were located within the trypsin-resistant amino-terminal third of the large F1 subunit. Only one of these epitopes was faithfully reproduced by a short synthetic peptide; the others might require specific local conformations to react with MAbs. The second antigenic site was located in a trypsin-sensitive domain of the F1 subunit towards the carboxy-terminal end of the cysteine-rich region. One of these epitopes was reproduced by synthetic peptides. In addition, mutagenized F protein with a substitution of serine for arginine at position 429 did not bind MAbs to the second site. These results are discussed in terms of F protein structure and the mechanisms of virus neutralization.
Arbiza
J
J
Servicio de Biologia Molecular, Instituto de Salud Carlos III, Madrid, Spain.
Taylor
G
G
López
J A
JA
Furze
J
J
Wyld
S
S
Whyte
P
P
Stott
E J
EJ
Wertz
G
G
Sullender
W
W
Trudel
M
M
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015707:HN Protein; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009500:Neutralization Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000472:pathogenicity; D010253:Respirovirus Infections / Q000517:prevention & control; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins; D014774:Virulence
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D015707:HN Protein; D009842:Oligopeptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G