The herpes simplex virus procapsid: structure, conformational changes upon maturation, and roles of the triplex proteins VP19c and VP23 in assembly

J Mol Biol. 1996 Nov 1;263(3):447-62. doi: 10.1016/s0022-2836(96)80018-0.

Abstract

The proteins coded by the five major capsid genes of herpes simplex virus 1, VP5 (gene UL19), VP19c (UL38), VP23 (UL18), pre-VP22a (UL26.5), and pre-VP21 (UL26), assemble into fragile roundish "procapsids", which mature into robust polyhedral capsids in a transition similar to that undergone by bacteriophage proheads. Here we describe the HSV-1 procapsid structure to a resolution of approximately 2.7 nm from three-dimensional reconstructions of cryo-electron micrographs. Comparison with the mature capsid provides insight into the large-scale conformational changes that take place upon maturation. In the procapsid, the elongated protomers (VP5 subunits) make little contact with each other except around the bases of the hexons and pentons, whereas they are tightly clustered into capsomers in the mature state; the axial channels, which are constricted or blocked in the mature capsid, are fully open; and unlike the well observed 6-fold symmetry of mature hexons, procapsid hexons are distorted into oval and triangular shapes. These deformations reveal a VP5 domain in the inner part of the protrusion wall which participates in inter-protomer bonding in the procapsid and is close to the site where the channel closes upon maturation. Remarkably, there are no direct contacts between neighboring capsomers; instead, interactions between them are mediated by the "triplexes" at the sites of local 3-fold symmetry. This observation discloses the mechanism whereby the triplex proteins, VP19c and VP23, play their essential roles in capsid morphogenesis. In the mature capsid, density extends continuously between neighboring capsomers in the inner "floor" layer. In contrast, there are large gaps in the corresponding region of the procapsid, implying that formation of the floor involves extensive remodeling. Inside the procapsid shell is the hollow spherical scaffold, whose radial density profile indicates that the major scaffold protein, pre-VP22a, is a long molecule (> 24 nm) composed of three domains. Since no evidence of icosahedral symmetry is detected in the scaffold, we infer that (unless higher resolution is required) the scaffold may not be an icosahedral shell but may instead be a protein micelle with a preferred radius of curvature.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Capsid / chemistry
  • Capsid / physiology
  • Capsid / ultrastructure*
  • Capsid Proteins
  • Epitopes / ultrastructure
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 1, Human / physiology
  • Herpesvirus 1, Human / ultrastructure*
  • Humans
  • Image Processing, Computer-Assisted
  • Microscopy, Electron / methods
  • Precipitin Tests
  • Protein Conformation
  • Viral Proteins
  • Virus Assembly / physiology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes
  • UL19 protein, simplexvirus
  • VP19 protein, Human herpesvirus 1
  • VP23 protein, Human herpesvirus 1
  • VP5 protein, Herpes simplex virus type 1
  • Viral Proteins