Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection

Cell Mol Life Sci. 2013 Apr;70(7):1297-306. doi: 10.1007/s00018-012-1213-0. Epub 2012 Nov 25.


Like most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM, and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed: vesicles in clusters (ViCs), contiguous vesicles (CVs), and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cell Membrane / ultrastructure*
  • Cell Membrane / virology*
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Hepacivirus / physiology*
  • Hepatitis C / pathology*
  • Host-Pathogen Interactions / physiology*
  • Humans
  • Imaging, Three-Dimensional
  • Intracellular Membranes / metabolism
  • Intracellular Membranes / ultrastructure
  • Intracellular Membranes / virology
  • Microscopy, Electron
  • Models, Biological
  • Protein Binding
  • RNA, Viral / metabolism
  • Tumor Cells, Cultured
  • Viral Proteins / metabolism
  • Viral Proteins / physiology
  • Virus Replication / physiology


  • RNA, Viral
  • Viral Proteins