Molecular epidemiology of mumps viruses in the Netherlands, 2017-2019

Abstract

Mumps cases continue to occur, also in countries with a relatively high vaccination rate. The last major outbreaks of mumps in the Netherlands were in 2009-2012 and thereafter, only small clusters and single cases were reported. Molecular epidemiology can provide insights in the circulation of mumps viruses. The aims of the present study were to analyze the molecular epidemiology of mumps viruses in the Netherlands in 2017-2019 and to compare the phylogenetic trees built from sequence data of near complete mumps virus genomes or from the SH gene and non-coding regions (SH+NCRs). To this end, Sanger sequence data from SH+NCRs were analyzed from 82 mumps genotype G viruses. In addition, near complete genomes were obtained from 10 mumps virus isolates using next-generation sequencing. Analysis of SH+NCRs sequences of mumps genotype G viruses revealed the presence of two major genetic lineages in the Netherlands, which was confirmed by analysis of near complete genomes. Comparison of phylogenetic trees built with SH+NCRs or near complete genomes indicated that the topology was similar, while somewhat longer branches were present in the phylogenetic tree with near complete genomes. These results confirm that analysis of SH + NCRs sequence data is a useful approach for molecular surveillance. Furthermore, data from recent mumps genotype G viruses might indicate (intermittent) circulation of mumps genotype G viruses in the Netherlands in 2017-2019.

Fig 1. Phylogenetic analysis of concatenated sequence data of SH and NCRs of mumps viruses detected in the Netherlands from 2017–2019 using the maximum likelihood method.

For this phylogenetic analysis, the transition model (TIM) +F+I was the best-fit model according to BIC. Only bootstrap values ≥95 are indicated. The phylogenetic tree was rooted using MuVi/London.GBR/3.02. The main genetic lineages of mumps viruses detected in the Netherlands are indicated with I, II and III, while mumps viruses collected from cases from which it was known that they were not infected in the Netherlands are indicated with ‘i’ (import) behind the virus name. Viruses from which also near complete genomes were obtained after isolation, are indicated with ‘fg’, while reference viruses are indicated with ‘r’.

Fig 2. Comparison of phylogenetic topology obtained by analysis of near complete genomes and SH+NCRs.

Phylogenetic analysis was performed on near complete genomes of isolates of mumps genotype G viruses and results were compared with SH+NCRs data obtained from the same set of mumps viruses detected in clinical materials (A) and in isolates (B). Phylogenetic trees were built with the maximum likelihood method and the generable time reversible (GTR)+ F+G4 model was used based on selection as the best-fit model according to BIC for the analysis of near complete genomes. Both trees were rooted using MuV/Iowa.USA/06/6. Only bootstrap values ≥95 are indicated.

Fig 3. Phylogenetic analysis of complete mumps virus genomes.

Phylogenetic analysis was performed on near complete genomes (excluding 3’ and 5’ termini) of mumps virus isolates detected in the Netherlands and various closely related and representative mumps viruses using GTR+F+G4 model based on analysis using ModelFinder [26]. Only bootstrap values ≥95 are indicated. Mumps viruses detected in the Netherlands are indicated in bold. Genotypes to which these viruses belong are indicated and the tree was rooted using Mumps virus Jeryl-Lynn (major strain).