High epidemic burden of RSV disease coinciding with genetic alterations causing amino acid substitutions in the RSV G-protein during the 2016/2017 season in The Netherlands

J Clin Virol. 2019 Mar:112:20-26. doi: 10.1016/j.jcv.2019.01.007. Epub 2019 Jan 23.

Abstract

Background: We found amino acid substitutions in the Gglycoprotein of respiratory syncytial virus (RSV) A during the 2016/2017 epidemic in The Netherlands.

Objectives: We evaluated whether these alterations led to increased RSV incidence and disease burden.

Study design: We sequenced the gene encoding the G-protein of prospectively collected clinical specimens from secondary care adult patients testing positive for RSV during the 2016/2017 and 2017/2018 epidemic RSV season. We evaluated associations between genetic, clinical and epidemiological data.

Results: We included 49 RSV strains. In 2016/2017 28 strains were included, 20 community acquired RSV-A, 5 hospital acquired RSV-A and 3 community acquired RSV-B. In 2017/2018 21 strains were included, 8 community acquired RSV-A and 13 community acquired RSV-B. G-proteins of 10 out of the 20 community acquired 2016/2017 RSV-A strains shared a set of eight novel amino acid substitutions of which seven in mucin-like regions 1 and 2 and one in the heparin binding domain. This genetic variant was no longer detected among 2017/2018 RSV-A strains. Among patients carrying the novel RSV-A strain-type, 30% died.

Conclusions: A set of eight amino acid substitutions was found in 50% of the 2016/2017 community acquired RSV-A G-proteins. This combination of substitutions was globally never observed before. The appearance of this new strain-type coincided with an increased RSV peak in The Netherlands and was associated with higher disease severity. The transient character of this epidemic strain-type suggests rapid clearance of this lineage in our study community.

Keywords: G-glycoprotein; Genetics; Mutations; RSV.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution*
  • Epidemics / statistics & numerical data
  • Female
  • Genetic Variation*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Netherlands / epidemiology
  • Phylogeny
  • RNA, Viral / genetics
  • Respiratory Syncytial Virus Infections / epidemiology*
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Virus, Human / genetics*
  • Respiratory Syncytial Virus, Human / pathogenicity
  • Sequence Analysis, DNA
  • Viral Fusion Proteins / genetics*

Substances

  • G glycoprotein, Respiratory syncytial virus
  • RNA, Viral
  • Viral Fusion Proteins