Identification of variable domains of the attachment (G) protein of subgroup A respiratory syncytial viruses

Abstract

We have previously classified isolates from a respiratory syncytial (RS) virus epidemic into distinct lineages by restriction mapping and nucleotide sequencing of parts of the nucleocapsid protein and small hydrophobic protein genes, which are areas of the genome not considered to be under immunological pressure. This study has now been extended by the determination of the nucleotide sequences of the attachment (G) protein genes of isolates from each subgroup A lineage. Deduced amino acid identities of the G proteins ranged between 80% and 99%, corresponding closely to the previously determined relatedness of the lineages. The amino acid variability was not evenly distributed; in the extracellular part of the protein there was a sharply defined hypervariable domain which was separated from a more extended variable domain by a highly conserved region. Most nucleotide changes in the variable domains were in the first and second positions of the codon triplets. These results suggest that there may be considerable immunological pressure for change in certain areas of the G protein and this may account for the ability of this virus to reinfect individuals repeatedly. The results presented here reflect the pattern of published data comparing prototype strains of the A and B subgroups.

Molecular epidemiology and genetic variability of respiratory syncytial virus (RSV) in Stockholm, 2002–2003

“…¼ number/year from Kenya [Scott et al, 2004], CH09, CH17, CH34, CH57 from USA [Peret et al, 1998], Mon/no./year from Uruguay and Mad/no./year from Spain [Garcia et al, 1994], Birm/no./year from Great Britain [Zambon et al, 2001], RSB/89-no. from Great Britain [Cane et al, 1991] and reference stains A2 [Wertz et al, 1985] and Long [Johnson et al, 1987]. Only bootstrap values greater than 50% are shown.…”

“…The G protein coding gene is one of the most genetically variable regions of the genome [Johnson et al, 1987;Sullender, 2000;Cane, 2001]. The G gene consists of two variable parts, the N-terminal and the C-terminal, and a central, conserved region [Johnson et al, 1987;Cane et al, 1991;Sullender et al, 1991;Sullender, 2000;Cane, 2001]. Most frequently, genotype classification of RSV makes use of the C-terminal region of the G gene [Peret et al, 1998[Peret et al, , 2000Venter et al, 2001;Zlateva et al, 2005].…”

Determination of the disulfide bond arrangement of human respiratory syncytial virus attachment (G) protein by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry

“…This region also has a sequence of 13 amino acids, including two of the conserved Cys residues (Fig. l), which is identical in all wild-type isolates of RSV that infect humans (Satake et al, 1985;Wertz et al, 1985;Johnson et al, 1987;Sullender et al, 1990Cane et al, 1991;Collins, 1991Collins, , 1996Garcia et al, 1994).…”

Genetic Variability and Molecular Epidemiology of Respiratory Syncytial Virus Subgroup A Strains in Japan Determined by Heteroduplex Mobility Assay

“…Among viral surface antigens, the attachment G glycoprotein (G protein) has the greatest antigenic diversity between these two groups and among strains within each group. The G-protein variability is concentrated in its ectodomain, which contains two hypervariable regions separated by a conserved 11-amino-acid motif (4,7,19,29). Recent molecular epidemiological studies suggest that many distinct RSV genotypes circulate worldwide and that similar genetic variants are clustered by time rather than by geographic location (6,8,17,26).…”

“…Genetic variability of RSV has most often been studied by using restriction fragment length polymorphism (RFLP) analysis and DNA sequencing (4,30). RFLP analysis is relatively easy to perform, although genotypes obtained by this method provide limited information.…”