Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication

• Published in: PloS one 2012-03, Vol.7 (3), p.e32807
• Main Authors: Eshaghi, Alireza, Duvvuri, Venkata R, Lai, Rachel, Nadarajah, Jeya T, Li, Aimin, Patel, Samir N, Low, Donald E, Gubbay, Jonathan B
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Analysis; Avidity; Biology; Child, Preschool; Children; Cladistic analysis; Cluster Analysis; Codons; DNA polymerase; Drosophila melanogaster; Escherichia coli; Foot & mouth disease; Gene Duplication; Gene sequencing; Genes; Genetic aspects; Genetic variability; Genetic Variation; Genotype; Glycoproteins; Glycosylation; Health aspects; Humans; Infant; Infection; Infections; Laboratories; Mediation; Medicine; Molecular Sequence Data; Ontario; Pathogenicity; Pathogens; Phylogeny; Regression analysis; Reproduction (copying); Respiratory syncytial virus; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Human - classification; Respiratory Syncytial Virus, Human - genetics; Respiratory Syncytial Virus, Human - isolation & purification; Respiratory tract diseases; Ribonucleic acid; RNA; RNA, Viral - chemistry; Sequence Alignment; Strains (organisms); Sugar; Variability; Viral Fusion Proteins - genetics; Virulence; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032807

Human respiratory syncytial virus (HRSV) is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010-2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV isolates studied, RSV-A (55.7%) was more commonly observed than RSV-B (42.3%). 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2%) clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10%) NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G) glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.