Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 13;7(2):veab071.
doi: 10.1093/ve/veab071. eCollection 2021 Sep.

Global spatiotemporal transmission patterns of human enterovirus 71 from 1963 to 2019

Bing Xu  1   2   3   4 , Jinfeng Wang  2   3 , Bin Yan  2   3 , Chengdong Xu  2 , Qian Yin  2 , Deyan Yang  5
Affiliations

Global spatiotemporal transmission patterns of human enterovirus 71 from 1963 to 2019

Bing Xu et al. Virus Evol. .

Abstract

Enterovirus 71 (EV71) can cause large outbreaks of hand, foot, and mouth disease (HFMD) and severe neurological diseases, which is regarded as a major threat to public health, especially in Asia-Pacific regions. However, the global spatiotemporal spread of this virus has not been identified. In this study, we used large sequence datasets and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of different EV71 subgroups globally. The study found that subgroups of HFMD presented global spatiotemporal variation, subgroups B0, B1, and B2 have caused early infections in Europe and America, and then subgroups C1, C2, C3, and C4 replaced B0-B2 as the predominant genotypes, especially in Asia-Pacific countries. The dispersal patterns of genotype B and subgroup C4 showed the complicated routes in Asia and the source might in some Asian countries, while subgroups C1 and C2 displayed more strongly supported pathways globally, especially in Europe. This study found the predominant subgroup of EV71 and its global spatiotemporal transmission patterns, which may be beneficial to reveal the long-term global spatiotemporal transmission patterns of human EV71 and carry out the HFMD vaccine development.

Keywords: enterovirus 71; foot; hand; mouth disease; phylogeographic analysis; spatial transmission.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1.
Figure 1.
Geographical distribution of EV71 genogroups. Different colors represented the number of isolates.
Figure 2.
Figure 2.
Phylogenetic analysis of EV71 VP1 gene sequences. The tree topology has been chosen to maximize the product of node posterior probabilities. Note: The branch colors meant the location of these strains. Branch lengths are scaled in units of time, as indicated by the time axis, with the branches colored by different countries. The thickness of the line represents the posterior probability. Thicker line represented higher posterior probability.
Figure 3A.
Figure 3A.
(A) Phylogenetic analysis of EV71 genotype B VP1 gene sequences. The tree topology has been chosen to maximize the product of node posterior probabilities. The upper left was the root location state posterior probability distributions. Note: The branch colors meant the location of these strains. Branch lengths are scaled in units of time, as indicated by the time axis with the branches colored by different countries. The thickness of the line represents the posterior probability. Thicker line represented higher posterior probability. (B) Phylogenetic analysis of EV71 genotype C VP1 gene sequences. The tree topology has been chosen to maximize the product of node posterior probabilities.
Figure 3B.
Figure 3B.
(A) Phylogenetic analysis of EV71 genotype B VP1 gene sequences. The tree topology has been chosen to maximize the product of node posterior probabilities. The upper left was the root location state posterior probability distributions. Note: The branch colors meant the location of these strains. Branch lengths are scaled in units of time, as indicated by the time axis with the branches colored by different countries. The thickness of the line represents the posterior probability. Thicker line represented higher posterior probability. (B) Phylogenetic analysis of EV71 genotype C VP1 gene sequences. The tree topology has been chosen to maximize the product of node posterior probabilities.
Figure 4.
Figure 4.
Root state posterior probability of EV71 genotype C.
Figure 5.
Figure 5.
Strong temporal signal tested in TempEst of EV71 genotype B (A) and genotype C (B).
Figure 6.
Figure 6.
Bayesian skyline plots of genotype EV71 B and C, showing population size (y-axis) through time (x-axis).
Figure 7.
Figure 7.
Spatial diffusion pathways of EV71 genotype B.
Figure 8.
Figure 8.
Spatial diffusion pathways of EV71 subgroup C1.
Figure 9.
Figure 9.
Spatial diffusion pathways of EV71 subgroup C2.
Figure 10.
Figure 10.
Spatial diffusion pathways of EV71 subgroup C4.
See this image and copyright information in PMC

References

    1. AbuBakar S. et al. (1999) ‘Identification of Enterovirus 71 Isolates from an Outbreak of Hand, Foot and Mouth Disease (HFMD) with Fatal Cases of Encephalomyelitis in Malaysia’, Virus Research, 61: 1–9. - PubMed
    1. ——— et al. (2009) ‘Enterovirus 71 Outbreak, Brunei’, Emerging Infectious Diseases, 15: 79–82. - PMC - PubMed
    1. Alexander J. P. et al. (1997) ‘Enterovirus 71 Infections and Neurologic Disease—United States, 1977–1991’, The Journal of Infectious Diseases, 169: 905–8. - PubMed
    1. Bessaud M. et al. (2014) ‘Molecular Comparison and Evolutionary Analyses of VP1 Nucleotide Sequences of New African Human Enterovirus 71 Isolates Reveal a Wide Genetic Diversity’, PLoS One, 9: e90624. - PMC - PubMed
    1. Bielejec F. et al. (2011) ‘SPREAD: Spatial Phylogenetic Reconstruction of Evolutionary Dynamics’, Bioinformatics, 27: 2910–2. - PMC - PubMed