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.
The integration of a protein's structure with its known sequence variation provides insight on how that protein evolves, for instance in terms of (changing) function or immunogenicity. Yet, collating the corresponding sequence variants into a multiple sequence alignment, calculating each position's conservation, and mapping this information back onto a relevant structure is not straightforward. We therefore built the Sequence Conservation on Protein 3D structure (scop3D) tool to perform these tasks automatically. The output consists of two modified PDB files in which the B-values for each position are replaced by the percentage sequence conservation, or the information entropy for each position, respectively. Furthermore, text files with absolute and relative amino acid occurrences for each position are also provided, along with snapshots of the protein from six distinct directions in space. The visualization provided by scop3D can for instance be used as an aid in vaccine development or to identify antigenic hotspots, which we here demonstrate based on an analysis of the fusion proteins of human respiratory syncytial virus and mumps virus.
Objectives: Mumps used to affect children between 2 and 15 years old. The mumpsemeasleserubella (MMR) vaccine is available, with vaccine coverage rate of about 85% after two vaccine doses. Recently new mumps outbreaks have emerged in highly vaccinated populations; the causes for these new outbreaks are yet unknown. We tested if a difference in seroneutralizing capacity against the vaccine and wild-type viruses existed and if waning immunity could be detected. Methods: In this study, 570 serum samples (age group 2e3 years (n ¼ 96), 8e9 years (n ¼ 95), 13 e14 years (n ¼ 94), 18e20 years (n ¼ 96), 24e26 years (n ¼ 92) and 50 þ years (n ¼ 97)) in Belgium were tested in the rapid fluorescent foci inhibition test for their neutralizing capacity against the vaccine and wild-type viruses. Results: Neutralizing antibodies against the vaccine strain were present in 84% (81/97) of the 2e3-year, 74% (70/95) of the 8e9-year, 81% (76/94) of the 13e14-year, 76% (73/96) of the 18e20-year, 67% (62/92) of the 24e26-year and 77% (75/97) of the 50þ-year age group serum samples. For all age groups, only about half of these serum samples were also positive for the wild-type virus. The geometric mean titres for the vaccine and wild-type virus for all younger age groups, except for 24e26 years, were significantly different, demonstrating poor in vitro cross-neutralization. Conclusions: A possible contribution of antigenic differences between the genotype A and G mumps virus as well as other immune factors, in addition to lower-than-optimal vaccination coverage and waning immunity, could explain the poor in vitro cross-neutralization and should be further studied.
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