Respiratory syncytial virus A in haematological patients with prolonged shedding: Premature stop codons and deletion of the genotype ON1 72-nucleotide-duplication in the attachment G gene.

Respiratory syncytial virus (RSV) can be associated with severe disease and prolonged shedding in immunocompromised patients. To investigate the genetic variability of RSV in consecutive samples of haematological patients with prolonged RSV shedding. Haematological patients at the University Hospital Heidelberg are routinely screened for respiratory viruses during winter season. In patients with prolonged RSV shedding between 2011 and 2014, Sanger-sequencing of the second hypervariable region of the RSV G gene was performed in consecutive samples. Further, deep-sequencing was performed in representative samples. Patients with prolonged RSV-A shedding were analysed (n=16, mean shedding 90days, 81.2% male). Phylogenetic analysis identified RSV genotypes NA1 (2011/12) or ON1 (2012/13). In most patients (n=12/16), Sanger-sequencing of the G gene showed identical sequences over the course of the shedding period. However, in two patients with particularly long viral shedding (333 and 142days), Sanger-sequencing revealed the presence of mutations leading to premature stop codons (37 and 70 amino acids truncated) in the G gene. In one additional patient, deep-sequencing revealed variants with premature stop codons at different positions. All three patients received repeatedly intravenous immunoglobulins. Interestingly, deep-sequencing revealed also a loss of the characteristic 72-nucleotide-duplication in all analysed ON1 strains. Long shedding periods and lack of immune selective pressure in the immunocompromised host seems to allow the persistence of viruses stripping a part of the C-terminus of the G glycoprotein. The loss of the characteristic 72-nucleotide-duplication in RSV-A ON1 variant strains is here described for the first time.

Tabatabai J ，Thielen A ，Lehners N ，Daeumer M ，Schnitzler P ... -  《-》

Co-Circulation of 72bp Duplication Group A and 60bp Duplication Group B Respiratory Syncytial Virus (RSV) Strains in Riyadh, Saudi Arabia during 2014.

Ahmed A ，Haider SH ，Parveen S ，Arshad M ，Alsenaidy HA ，Baaboud AO ，Mobaireek KF ，AlSaadi MM ，Alsenaidy AM ，Sullender W ... -  《PLoS One》

Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.

Eshaghi A ，Duvvuri VR ，Lai R ，Nadarajah JT ，Li A ，Patel SN ，Low DE ，Gubbay JB ... -  《PLoS One》

Molecular epidemiology of respiratory syncytial virus for 28 consecutive seasons (1990-2018) and genetic variability of the duplication region in the G gene of genotypes ON1 and BA in South Korea.

Yun KW ，Choi EH ，Lee HJ 《-》

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

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.

Al-Hassinah S ，Parveen S ，Somily AM ，AlSaadi MM ，Alamery SF ，Haq SH ，Alsenaidy HA ，Ahmed A ... -  《-》