Genetic heterogeneity of the attachment glycoprotein G among group A respiratory syncytial viruses

Fifteen independent group A respiratory syncytial virus (RSV) isolates were compared by sequencing a 300-nucleotide interval encoding a variable region of the attachment glycoprotein G. The viruses compared included the reference strains Long (USA 1956), A2 (Australia 1961), and 669 (Sweden 1959), along with 13 clinical isolates obtained at different times and locations throughout the United States. Representatives of all six antigenic subgroups, recognized by reactivity patterns with monoclonal antibodies, were compared. The maximum sequence heterogeneity within the G glycoprotein region compared was 15.7% of nucleotide sequences and 26% of amino acid sequences, more than twice the difference observed between Long and A2. Half of the nucleotide changes encoded amino acid substitutions, possibly indicating that the protein interval compared was subject to immune selection. Because the ratio of nucleotide to amino acid substitutions was nearly constant for all degrees of genetic divergence, the potential range of sequence divergence among group A RSV has probably not yet been attained. There was little correlation between the patterns of reactivity against a panel of monoclonal antibodies and sequence relationships among the 15 isolates. The sequence information showed multiple genotypes circulating simultaneously in the same community and very similar genotypes circulating in widely separated communities and during different years. Genetic analyses of RSV strains can provide important information about the relationships between RSV infections.