Abstract
The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection. We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957–1982) with mumps virus genotype G strains (from 2004 onwards). Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan. Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein. There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein. These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains. We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis. These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.
Highlights
The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection
A phylogenetic analysis based on the small hydrophobic (SH) gene sequences was performed to determine the genotypes of the samples from recent outbreaks in the Netherlands (n = 110), as previously described[27], and from a collection of historic wild type strains isolated from Dutch patients since 1954 (n = 46) (Fig. 1)
Two historic wild type strains belong to genotype A, including a strain that is identical to MuVi/Boston.USA/0.45 “Enders”, the mumps prototype strain that was isolated from a patient in the USA
Summary
The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection. There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains. We found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities. Vaccine-induced antibodies neutralize genotype G strains, the level of neutralization is lower than for the vaccine strain (Rubin et al 2008; Dayan & Rubin 2008; Gouma et al 2016)[12,23,24] This raises questions about the biological consequences of amino acid differences between genotype G and vaccine strains at sites that are important for immune recognition and pathogenesis. Differences were observed in regions that may play a role in mumps virus pathogenesis
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