Dataset Information

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

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.

SUBMITTER: Xu B

PROVIDER: S-EPMC9927877 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Xu Bing B Wang Jinfeng J Yan Bin B Xu Chengdong C Yin Qian Q Yang Deyan D

Virus evolution 20210813 2

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 foun ...[more]

PMID: 36819972

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Project description:UNLABELLED:Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children, and structural characterization of EV71 during its life cycle can aid in the development of therapeutics against HFMD. Here, we present the atomic structures of the full virion and an uncoating intermediate of a clinical EV71 C4 strain to illustrate the structural changes in the full virion that lead to the formation of the uncoating intermediate prepared for RNA release. Although the VP1 N-terminal regions observed to penetrate through the junction channel at the quasi-3-fold axis in the uncoating intermediate of coxsackievirus A16 were not observed in the EV71 uncoating intermediate, drastic conformational changes occur in this region, as has been observed in all capsid proteins. Additionally, the RNA genome interacts with the N-terminal extensions of VP1 and residues 32 to 36 of VP3, both of which are situated at the bottom of the junction. These observations highlight the importance of the junction for genome release. Furthermore, EV71 uncoating is associated with apparent rearrangements and expansion around the 2- and 5-fold axes without obvious changes around the 3-fold axes. Therefore, these structures enabled the identification of hot spots for capsid rearrangements, which led to the hypothesis that the protomer interface near the junction and the 2-fold axis permits the opening of large channels for the exit of polypeptides and viral RNA, which is an uncoating mechanism that is likely conserved in enteroviruses. IMPORTANCE:Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children. EV71 contains an RNA genome protected by an icosahedral capsid shell. Uncoating is essential in EV71 life cycle, which is characterized by conformational changes in the capsid to facilitate RNA release into host cell. Here we present the atomic structures of the full virion and an uncoating intermediate of a clinical C4 strain of EV71. Structural analysis revealed drastic conformational changes associated with uncoating in all the capsid proteins near the junction at the quasi-3-fold axis and protein-RNA interactions at the bottom of the junction in the uncoating intermediate. Significant capsid rearrangements also occur at the icosahedral 2- and 5-fold axes but not at the 3-fold axis. Taking the results together, we hypothesize that the junction and nearby areas are hot spots for capsid breaches for the exit of polypeptides and viral RNA during uncoating.

Dataset Information

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

Publications

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

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