Premature stop codons in the G glycoprotein of human respiratory syncytial viruses resistant to neutralization by monoclonal antibodies.
Mutants of human respiratory syncytial (RS) virus which escaped neutralization by monoclonal antibodies directed against the G glycoprotein were selected from the Long strain. Most mutants showed drastic antigenic changes, reflected in the lack of reactivity with several anti-G antibodies, including the one used for selection. Sequence analysis revealed the presence of in-frame premature stop codons in the mutated G genes which shortened the G polypeptide by between 11 and 42 amino acids. In contrast, two mutants selected with monoclonal antibody 25G contained two amino acid substitutions (Phe-265----Leu and Leu-274----Pro) and had lost only the capacity to bind the antibody used in their selection. These results demonstrate that the carboxy-terminal end of the G molecule is dispensable for infectivity in tissue culture and indicate the importance of this part of the G protein in determining its antigenicity.
Rueda
P
P
Servicio de Biología Molecular, Centro Nacional de Microbiología, Madrid, Spain.
Delgado
T
T
Portela
A
A
Melero
J A
JA
García-Barreno
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology*; D003062:Codon; D005814:Genes, Viral; D015707:HN Protein; D006801:Humans; D009154:Mutation; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000737:chemistry; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D014764:Viral Proteins
D000911:Antibodies, Monoclonal; D003062:Codon; D015707:HN Protein; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G