Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress

Elife. 2020 Jun 24:9:e56627. doi: 10.7554/eLife.56627.

Abstract

During herpesvirus infection, egress of nascent viral capsids from the nucleus is mediated by the viral nuclear egress complex (NEC). NEC deforms the inner nuclear membrane (INM) around the capsid by forming a hexagonal array. However, how the NEC coat interacts with the capsid and how curved coats are generated to enable budding is yet unclear. Here, by structure-guided truncations, confocal microscopy, and cryoelectron tomography, we show that binding of the capsid protein UL25 promotes the formation of NEC pentagons rather than hexagons. We hypothesize that during nuclear budding, binding of UL25 situated at the pentagonal capsid vertices to the NEC at the INM promotes formation of NEC pentagons that would anchor the NEC coat to the capsid. Incorporation of NEC pentagons at the points of contact with the vertices would also promote assembly of the curved hexagonal NEC coat around the capsid, leading to productive egress of UL25-decorated capsids.

Keywords: capsid budding; herpes simplex virus type 1; herpesvirus; infectious disease; membrane budding; microbiology; nuclear egress; nuclear egress complex; virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism*
  • Cloning, Molecular
  • Cryoelectron Microscopy
  • Escherichia coli
  • Gene Expression Regulation, Viral / physiology*
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism*
  • Microscopy, Confocal
  • Protein Transport
  • Virus Replication

Substances

  • Capsid Proteins