Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection

J Biol Chem. 2016 Jul 8;291(28):14815-25. doi: 10.1074/jbc.M115.711382. Epub 2016 May 16.


Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV.

Keywords: aMPV/B, fusogenicity; fusion protein; infection; integrin; membrane fusion; viral replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Fusion*
  • Cell Line
  • Metapneumovirus / physiology*
  • Paramyxoviridae Infections / physiopathology*
  • Paramyxoviridae Infections / virology
  • Receptors, Vitronectin / physiology*
  • Viral Fusion Proteins / physiology*
  • Virus Replication


  • Receptors, Vitronectin
  • Viral Fusion Proteins
  • integrin alphavbeta1

Associated data

  • PDB/4dag