Genetic Variability of Human Respiratory Syncytial Virus A Strains Circulating in Ontario: A Novel Genotype with a 72 Nucleotide G Gene Duplication

Alireza Eshaghi,Venkata R Duvvuri,Samir N Patel,Jeya T Nadarajah,Rachel Lai,Aimin Li,Donald E Low,Jonathan B Gubbay,Yury E Khudyakov

doi:10.1371/journal.pone.0032807

Alireza Eshaghi, Venkata R Duvvuri + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0032807

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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.

Highlights

Human Respiratory Syncytial virus (RSV) is the major cause of lower respiratory tract infection (LRTI) in infants and young children, and is responsible for a significant proportion of RTIs in the elderly
Among the 199 consecutive RSV isolates included in this study, 47 (23.6%) were obtained from patients reviewed in the emergency room but not hospitalized, 80 (40.2%) collected from hospitalized patients and 21 (10.6%) collected from an ambulatory community setting
In this study we analyzed G and F genes of 112 RSV-A isolates from clinical samples tested during winter 2010–2011 in Ontario, Canada

Summary

Introduction

Human Respiratory Syncytial virus (RSV) is the major cause of lower respiratory tract infection (LRTI) in infants and young children, and is responsible for a significant proportion of RTIs in the elderly. It causes repeated infections throughout life due to limited immune protection from earlier RSV exposure [1,2,3]. G and F are mainly involved in virus attachment to cell receptors and mediation of cell membrane fusion, respectively [6,7] Both proteins are highly accessible to neutralizing antibodies, with resultant accumulation of mutations in response to host immunological pressure [8]

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