In vitro assembly of virus-like particles of a gammaretrovirus, the murine leukemia virus XMRV

J Virol. 2012 Feb;86(3):1297-306. doi: 10.1128/JVI.05564-11. Epub 2011 Nov 16.

Abstract

Immature retroviral particles are assembled by self-association of the structural polyprotein precursor Gag. During maturation the Gag polyprotein is proteolytically cleaved, yielding mature structural proteins, matrix (MA), capsid (CA), and nucleocapsid (NC), that reassemble into a mature viral particle. Proteolytic cleavage causes the N terminus of CA to fold back to form a β-hairpin, anchored by an internal salt bridge between the N-terminal proline and the inner aspartate. Using an in vitro assembly system of capsid-nucleocapsid protein (CANC), we studied the formation of virus-like particles (VLP) of a gammaretrovirus, the xenotropic murine leukemia virus (MLV)-related virus (XMRV). We show here that, unlike other retroviruses, XMRV CA and CANC do not assemble tubular particles characteristic of mature assembly. The prevention of β-hairpin formation by the deletion of either the N-terminal proline or 10 initial amino acids enabled the assembly of ΔProCANC or Δ10CANC into immature-like spherical particles. Detailed three-dimensional (3D) structural analysis of these particles revealed that below a disordered N-terminal CA layer, the C terminus of CA assembles a typical immature lattice, which is linked by rod-like densities with the RNP.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cryoelectron Microscopy
  • DNA Primers
  • Escherichia coli / ultrastructure
  • Escherichia coli / virology
  • Fourier Analysis
  • Leukemia Virus, Murine / physiology*
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Proteolysis
  • Sequence Homology, Amino Acid
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism
  • Virion / physiology*
  • Virus Assembly*

Substances

  • DNA Primers
  • Viral Proteins