Variability in the glycoprotein G gene of RSV-A ON1 strains causing bronchiolitis

Abstract

<b>Background:</b> Respiratory syncytial virus (RSV)-A genotype ON1 caused a less severe bronchiolitis course than the previously circulating RSV-A genotype (Midulla, F et al JID 2018;219:526-534). However, ON1 continued to circulate worldwide and to differentiate in new strains. <b>Aim:</b> to study the variability of the viral glycoprotein G in relation to clinical severity in bronchiolitis cases. <b>Methods:</b> From prospectively enrolled previously healthy term infants hospitalized for bronchiolitis in 2012-13 to 2017-18 epidemic seasons, cases positive to RSV-A ON1 only were selected. After sequencing the second half of the G gene of about 70 samples, a phylogenetic analysis was performed. Demographic and clinical data were compared among divergent ON1 clades. <b>Results:</b> The phylogenetic analysis of the G gene identified genomic variants appearing since 2012; some of them were not maintained in the following seasons. All sequences did not present polymorphisms in the conserved tract of the G protein that binds the cellular receptor and in the heparin-binding domain. Nonetheless, most strains sequenced in the 2017-18 season set well apart from those of the previous epidemic seasons, in two distant branches of the phylogenetic tree. The two more divergent branches were characterized by patterns of aminoacid changes never reported before, some of which located in antigenic sites. Moreover, substitutions may have altered N- and O-glycosilation sites. Patients infected with divergent strains presented higher severity scores. <b>Conclusions:</b> The aminoacid changes detected in the hypervariable part of the G protein may have altered functions and/or changed its immunogenicity determining an impact on disease severity.