Calicivirus VP2 forms a portal-like assembly following receptor engagement

Nature. 2019 Jan;565(7739):377-381. doi: 10.1038/s41586-018-0852-1. Epub 2019 Jan 9.

Abstract

To initiate infection, many viruses enter their host cells by triggering endocytosis following receptor engagement. However, the mechanisms by which non-enveloped viruses escape the endosome are poorly understood. Here we present near-atomic-resolution cryo-electron microscopy structures for feline calicivirus both undecorated and labelled with a soluble fragment of its cellular receptor, feline junctional adhesion molecule A. We show that VP2, a minor capsid protein encoded by all caliciviruses1,2, forms a large portal-like assembly at a unique three-fold axis of symmetry, following receptor engagement. This assembly-which was not detected in undecorated virions-is formed of twelve copies of VP2, arranged with their hydrophobic N termini pointing away from the virion surface. Local rearrangement at the portal site leads to the opening of a pore in the capsid shell. We hypothesize that the portal-like assembly functions as a channel for the delivery of the calicivirus genome, through the endosomal membrane, into the cytoplasm of a host cell, thereby initiating infection. VP2 was previously known to be critical for the production of infectious virus3; our findings provide insights into its structure and function that advance our understanding of the Caliciviridae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calicivirus, Feline / chemistry
  • Calicivirus, Feline / growth & development
  • Calicivirus, Feline / metabolism*
  • Calicivirus, Feline / ultrastructure*
  • Capsid Proteins / chemistry
  • Capsid Proteins / metabolism*
  • Capsid Proteins / ultrastructure*
  • Cats
  • Cell Line
  • Cryoelectron Microscopy*
  • Endosomes / metabolism
  • Endosomes / virology
  • Genome, Viral
  • Hydrophobic and Hydrophilic Interactions
  • Junctional Adhesion Molecule A / chemistry
  • Junctional Adhesion Molecule A / metabolism
  • Junctional Adhesion Molecule A / ultrastructure*
  • Models, Molecular
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism
  • Receptors, Virus / ultrastructure*
  • Static Electricity
  • Virion / chemistry
  • Virion / genetics
  • Virion / metabolism
  • Virion / ultrastructure
  • Virus Assembly*

Substances

  • Capsid Proteins
  • Junctional Adhesion Molecule A
  • Receptors, Virus