Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4

Virology. 2014 Jun;458-459:125-35. doi: 10.1016/j.virol.2014.04.027. Epub 2014 May 13.

Abstract

Coronaviruses replicate their genomes in association with rearranged cellular membranes. The coronavirus nonstructural integral membrane proteins (nsps) 3, 4 and 6, are key players in the formation of the rearranged membranes. Previously, we demonstrated that nsp3 and nsp4 interact and that their co-expression results in the relocalization of these proteins from the endoplasmic reticulum (ER) into discrete perinuclear foci. We now show that these foci correspond to areas of rearranged ER-derived membranes, which display increased membrane curvature. These structures, which were able to recruit other nsps, were only detected when nsp3 and nsp4 were derived from the same coronavirus species. We propose, based on the analysis of a large number of nsp3 and nsp4 mutants, that interaction between the large luminal loops of these proteins drives the formation of membrane rearrangements, onto which the coronavirus replication-transcription complexes assemble in infected cells.

Keywords: Coronavirus; Membrane rearrangements; Nsps; Replication–transcription complex; Transmembrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Membrane
  • Conserved Sequence
  • Coronavirus / genetics
  • Coronavirus / metabolism*
  • Endoplasmic Reticulum / physiology
  • Endoplasmic Reticulum / virology
  • Gene Expression Regulation, Viral / physiology
  • Mice
  • Mutation
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication

Substances

  • Viral Nonstructural Proteins