Preliminary functional and phylogeographic analyses of the 72 nucleotide duplication region in the emerging human respiratory syncytial virus ON1 strain attachment glycoprotein gene

Abstract The emerging human respiratory syncytial virus (hRSV) ON1 strain, which is characterized by a 72-nt duplication in the attachment glycoprotein (G) gene, has replaced other prevailing global genotypes since its discovery in 2012. In this study, we used the pseudotype lentiviral system to directly address the effect of the duplication on hRSV infection. In addition, representative 199 ON1 sequences selected from 2599 ON1 sequences that were downloaded from GenBank were used to perform Bayesian skyline and phylogeographic analyses. Our results showed that lentiviral pseudoparticles mimicked the key functions of the G-protein on hRSV cell entry. Further, we showed that deletion of the G-protein duplication decreased the efficiency of pLV infection. The mean substitution rate of the second mucin-like highly variable region for the ON1 G-protein gene was 2.14 × 10−3 (95 % HPD: 1.23 × 10−3, 3.08 × 10−3) nucleotide substitutions per site per year. Phylogeographic analyses showed that the ON1 isolates might originate from Europe at the time of MRCA (i.e., the most recent common ancestors), which dated back to 1998.3 (95 % HPD: 1989.2, 2005.2). These preliminary findings revealed the enhanced attachment function of the duplication region in the ON1 G gene and highlighted the importance of ongoing surveillance of ON1 to better understand the molecular epidemiology of hRSV.