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

Background: Respiratory syncytial virus (RSV) can be associated with severe disease and prolonged shedding in immunocompromised patients. Objective: To investigate the genetic variability of RSV in consecutive samples of haematological patients with prolonged RSV shedding. Study design: Haematologic...

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Hauptverfasser: Tabatabai, Julia (VerfasserIn) , Giesen, Nicola (VerfasserIn) , Schnitzler, Paul (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2018
In: Clinical and diagnostic virology
Year: 2018, Jahrgang: 98, Pages: 10-17
ISSN:1873-4901
DOI:10.1016/j.jcv.2017.11.003
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1016/j.jcv.2017.11.003
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1386653217303116
Volltext
Verfasserangaben:J. Tabatabai, A. Thielen, N. Lehners, M. Daeumer, P. Schnitzler

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520 |a Background: Respiratory syncytial virus (RSV) can be associated with severe disease and prolonged shedding in immunocompromised patients. Objective: To investigate the genetic variability of RSV in consecutive samples of haematological patients with prolonged RSV shedding. Study design: 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. Results: 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. Conclusions: 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. 
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