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The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating

Shingler, KL and Yoder, JL and Carnegie, MS and Ashley, RE and Makhov, AM and Conway, JF and Hafenstein, S (2013) The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating. PLoS Pathogens, 9 (3). ISSN 1553-7366

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Abstract

Since its discovery in 1969, enterovirus 71 (EV71) has emerged as a serious worldwide health threat. This human pathogen of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. Upon binding to a host receptor on the cell surface, the virus begins a two-step uncoating process, first forming an expanded, altered "A-particle", which is primed for genome release. In a second step after endocytosis, an unknown trigger leads to RNA expulsion, generating an intact, empty capsid. Cryo-electron microscopy reconstructions of these two capsid states provide insight into the mechanics of genome release. The EV71 A-particle capsid interacts with the genome near the icosahedral two-fold axis of symmetry, which opens to the external environment via a channel ~10 Å in diameter that is lined with patches of negatively charged residues. After the EV71 genome has been released, the two-fold channel shrinks, though the overall capsid dimensions are conserved. These structural characteristics identify the two-fold channel as the site where a gateway forms and regulates the process of genome release. © 2013 Shingler et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shingler, KL
Yoder, JL
Carnegie, MS
Ashley, RE
Makhov, AMamm241@pitt.eduAMM241
Conway, JFJames.Conway@pitt.eduJXC100
Hafenstein, S
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorRey, Félix A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 15 April 2013
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 9
Number: 3
DOI or Unique Handle: 10.1371/journal.ppat.1003240
Schools and Programs: School of Medicine > Structural Biology
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 08 Apr 2013 16:55
Last Modified: 05 Feb 2019 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/17887

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