Virus and cell fusion mechanisms

Annu Rev Cell Dev Biol. 2014;30:111-39. doi: 10.1146/annurev-cellbio-101512-122422. Epub 2014 Jun 27.


In biomembrane fusion pathways, membranes are destabilized through insertions of amphipathic protein segments, lipid reorganization via hemifusion, protein restructuring, and dimpling of the membranes. Four classes of membrane proteins are known in virus and cell fusion. Class I virus-cell fusion proteins (fusogens) are α-helix-rich prefusion trimers that form coiled-coil structures that insert hydrophobic fusion peptides or loops (FPs or FLs) into membranes and refold into postfusion trimers. Class II virus-cell fusogens are β-sheet-rich prefusion homo- or heterodimers that insert FLs into membranes, ending in postfusion trimers. Class III virus-cell fusogens are trimers with both α-helices and β-sheets that dissociate into monomers, insert FLs into membranes, and oligomerize into postfusion trimers. Class IV reoviral cell-cell fusogens are small proteins with FLs that oligomerize to fuse membranes. Class I cell-cell fusogens (Syncytins) were captured by mammals from retroviruses, and class II cell-cell fusogens (EFF-1/AFF-1) fuse membranes via homotypic zippering. Mechanisms and fusogens for most cell fusion events are unknown.

Keywords: Caenorhabditis elegans; enveloped viruses; fusion proteins; fusogen; hemifusion; placenta; reoviruses.

Publication types

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

MeSH terms

  • Animals
  • Cell Fusion*
  • Gene Products, env / physiology
  • Hemagglutinin Glycoproteins, Influenza Virus / physiology
  • Humans
  • Membrane Fusion*
  • Membrane Glycoproteins / physiology
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Pregnancy Proteins / physiology
  • Protein Conformation
  • Structure-Activity Relationship
  • Viral Envelope Proteins / physiology
  • Viral Fusion Proteins / chemistry
  • Viral Fusion Proteins / classification
  • Viral Fusion Proteins / physiology*
  • env Gene Products, Human Immunodeficiency Virus / physiology


  • G protein, vesicular stomatitis virus
  • Gene Products, env
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Membrane Glycoproteins
  • Pregnancy Proteins
  • Viral Envelope Proteins
  • Viral Fusion Proteins
  • env Gene Products, Human Immunodeficiency Virus
  • syncytin