The enterovirus 71 A-particle forms a gateway to allow genome release: a cryoEM study of picornavirus uncoating

PLoS Pathog. 2013 Mar;9(3):e1003240. doi: 10.1371/journal.ppat.1003240. Epub 2013 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid / physiology
  • Capsid / ultrastructure
  • Capsid Proteins / metabolism*
  • Cryoelectron Microscopy
  • Endocytosis
  • Enterovirus A, Human / genetics*
  • Enterovirus A, Human / metabolism
  • Enterovirus A, Human / pathogenicity*
  • Enterovirus A, Human / ultrastructure
  • Enterovirus Infections / virology
  • Genome, Viral*
  • HeLa Cells
  • Host-Pathogen Interactions*
  • Humans
  • Protein Binding
  • RNA, Viral / physiology
  • Receptors, Cell Surface / metabolism
  • Virion / genetics
  • Virus Uncoating / physiology*

Substances

  • Capsid Proteins
  • RNA, Viral
  • Receptors, Cell Surface

Grant support

The work was funded by a Junior Faculty Research Scholar Award, The Max Lang Scholar Award from Pennsylvania State University College of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.