Evolutionary analysis of the ON1 genotype of subtype a respiratory syncytial virus in Riyadh during 2008-16

Abstract

Respiratory syncytial virus is a leading cause of acute respiratory tract infection (ARI) in children worldwide. Limited information is available on molecular epidemiology of respiratory syncytial virus (RSV) from Saudi Arabia. An attempt was made to identify and characterize RSV strains in nasopharyngeal aspirates collected from hospitalized symptomatic ARI pediatric patients with <5 years of age from Riyadh, Saudi Arabia during 2016. All the samples (n = 100) were tested for RSV by real time PCR. The RSV strains were characterized by sequencing of the second hypervariable region of G protein gene. The study sequences along with the previously reported strains from Saudi Arabia were assessed for mutational, glycosylation, phylogenetic, selection pressure and entropy analyses. Fifty percent of the nasopharyngeal aspirates were positive for RSV. The RSVA (72%) predominated as compared to RSVB (24%) during the study. The study RSVA strains (n = 29) clustered into NA1 and ON1 genotypes whereas all the RSVB sequences (n = 5) were in BA genotype by phylogenetic analysis. Interestingly, 97% of RSVA sequences (n =28) clustered into ON1 genotype with 72 bp duplication in the G protein gene. Numerous mutations, variable N-/O-glycosylation sites and purifying selections were observed in the ON1 genotype. Positive selection with high entropy value was observed for three codons in ON1 (247, 262 and 274 amino acids) indicating higher probability of variations at these positions. Our study shows the progressive emergence and predominance of the ON1 genotype in Riyadh, Saudi Arabia during 2008-16. ON1 genotype almost replaced the previously circulating RSVA strains in this region during this period. Contribution of host genetic and immune factors towards disease severity of the ON1 genotype needs to be investigated in future studies. RSV surveillance in future elaborate investigations are needed in this region to understand its disease burden, evolutionary trajectory and circulation dynamics warranting steps towards vaccine development.

Keywords: ON1 and BA genotypes; Phylogenetic analysis; Respiratory syncytial virus; Saudi Arabia.