Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins

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.

Figure 1

Maximum parsimony tree based on SH gene sequences. Representation of classification of 46 mumps virus strains from the pre-vaccination era and 110 recent mumps virus strains, all indicated by thick lines. Percentages indicate bootstrap values (1000 replicates). All but one mumps virus strain were collected from Dutch patients, the non-Dutch strain was isolated from a patient from Albany, USA in 1954. Genotypes are labeled by color. Mumps virus sequences retrieved from GenBank (n = 78), including WHO reference strains (n = 27), are included in the phylogenetic tree and are indicated by thin lines.

Figure 2

Overview of the consensus and the variable sequences of the F and HN proteins. Variation sequence shows all changes observed for both genotypes. Accessibility for the consensus (ACC consensus) and for the variation sequence (ACC variation), entropy and abundance are expressed as percentages and indicated by colors, indicated by the legend at the bottom. Epitope regions (italic, red) and glycosylation patterns (bold, blue) are indicated on the sequences. Parts of the structures that were missing in the protein models are indicated with the light blue regions. The upper part represents the F protein, the lower part the HN protein.

Figure 3

Overview of important variable positions on both the HN and F protein, as described in the literature. (A) The F protein important functional regions with glycosylation sites (yellow), fusion promotion sites (orange), cleavage site (pink), neurovirulence (dark blue) and known B-cell epitope regions (green) mapped on the pre-fusion structure. Zoom is on the variation at position 97 (cyan blue) near the cleavage site (pink). (B) The HN protein with glycosylation sites (yellow), fusion promotion sites (orange), receptor-binding regions (pink), neuraminidase activity regions (cyan blue), Ca²⁺-binding sites (red), neurovirulence regions (dark blue), known T-cell epitope (purple) and known B-cell epitope regions (green) mapped on the structure. Zoom is on the variations at positions 354, 356 and 442 (brown positions).

Figure 4

In silico protein model of the F and HN protein with the specific functional regions mapped on the structures in different colors. (A) F protein with specific regions which are colored as described in the legend to Fig. 3. (B) HN protein with specific regions which are colored as described in the legend to Fig. 3.