Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design

Figures

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  Figure 1. Global temporal dynamics of the prevalence of various norovirus genotypes over a period between 1966 and 2019 (n = 26,469). The percentage of the top five genotypes each year was presented, and the remaining genotypes are calculated as others.

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  Figure 2. Phylogenetic trees and the corresponding root-to-tip divergence plots of the complete capsid genes (ORF2) of noroviruses. VP1-encoding nucleotide sequences of GII.4 (a), GII.4 from Zhengding surveillance (b), GII.2 (c), GII.3 (d), GII.6 (e) and GII.17 (f) genotypes are shown. The x-axis indicates the collection years, and the y-axis shows the root-to-tip divergence on the neighbor joining phylogenetic tree. The black line indicates a linear regression line of the root-to-tip divergence and collection years. Each circle presents a strain, and each color indicates a specific variant.

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  Figure 3. MCC tree based on complete capsid-encoding genes (ORF2s) of noroviruses. VP1-encoding nucleotide sequences of GII.4 (a), GII.4 from Zhengding surveillance (b), GII.2 (c), GII.3 (d), GII.6 (e) and GII.17 (f) genotypes. The trees were made using GTR + G + I nucleotide substitution model, an uncorrelated exponential clock (UCED) model and the Bayesian skyline as a tree prior. Each variant is shown by a specific color. A pandemic emergence of GII.4 is represented by the shaded area.

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  Figure 4. Predicted GII.4 norovirus evolving blockade epitopes. Bioinformatic approaches predicted five antibody epitopes on the surface of GII.4 noroviruses that appeared to be evolving over time and to correlate with the emergence of new GII.4 outbreak strains. (a) Amino acid variation of Epitopes A–E by GII.4 variant. (b) Surface representation of Sydney_2012 (brown) and GII.4c (grey). Epitope A (plum red), Epitope B (orange), Epitope C (lemon yellow), Epitope D (blue) and Epitope E (purple) are mapped onto P-dimer. (c) Cartoon representation of the subtle changes of blockade epitopes.