title: Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.
abstract: 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.
authors.affiliation: Ontario Agency for Health Protection and Promotion, Toronto, Ontario, Canada.
authors.forename: Alireza
authors.initials: A
authors.lastname: Eshaghi
authors.forename: Venkata R
authors.initials: VR
authors.lastname: Duvvuri
authors.forename: Rachel
authors.initials: R
authors.lastname: Lai
authors.forename: Jeya T
authors.initials: JT
authors.lastname: Nadarajah
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Gubbay
mesh_terms: D000595:Amino Acid Sequence; D002675:Child, Preschool; D016000:Cluster Analysis; D020440:Gene Duplication; D014644:Genetic Variation; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009864:Ontario; D010802:Phylogeny; D012367:RNA, Viral / Q000737:chemistry; D018357:Respiratory Syncytial Virus Infections / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D016415:Sequence Alignment; D014760:Viral Fusion Proteins / Q000235:genetics*
chemical_list: C502275:G glycoprotein, Respiratory syncytial virus; D012367:RNA, Viral; D014760:Viral Fusion Proteins