The three C-terminal residues of human respiratory syncytial virus G glycoprotein (Long strain) are essential for integrity of multiple epitopes distinguishable by antiidiotypic antibodies.

Recently isolated escape mutants of human respiratory syncytial virus (HRSV) are described. The mutants were selected after serial passage of the Long strain in the presence of monoclonal antibodies directed against the attachment (G) glycoprotein. The genetic changes associated to the mutant phenotype were nucleotide substitutions leading to either amino acid replacements or new stop codons that shorten the G polypeptide by one amino acid. Sequence changes within the three C-terminal residues of the G molecule abolished multiple epitopes, some of them being distinguished only by virus-binding inhibition of the corresponding antibodies with a panel of antiidiotypic antisera. These results extend previous studies that demonstrated the extreme capacity of HRSV to accommodate multiple sequence changes within the antigenically relevant G protein C-terminal third. These results are discussed in terms of both the antigenic structure of the G molecule and the generation of new antigenic variants that mimic natural variants of HRSV.