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.