Parainfluenza virus 5 m protein interaction with host protein 14-3-3 negatively affects virus particle formation

J Virol. 2011 Mar;85(5):2050-9. doi: 10.1128/JVI.02111-10. Epub 2010 Dec 8.


Paramyxovirus matrix (M) proteins organize virus assembly, linking viral glycoproteins and viral ribonucleoproteins together at virus assembly sites on cellular membranes. Using a yeast two-hybrid screening approach, we identified 14-3-3 as a binding partner for the M protein of parainfluenza virus 5 (PIV5). Binding in both transfected and PIV5-infected cells was confirmed by coimmunoprecipitation and was mapped to a C-terminal region within the M protein, namely, 366-KTKSLP-371. This sequence resembles known 14-3-3 binding sites, in which the key residue for binding is a phosphorylated serine residue. Mutation of S369 within the PIV5 M protein disrupted 14-3-3 binding and improved the budding of both virus-like particles (VLPs) and recombinant viruses, suggesting that 14-3-3 binding impairs virus budding. 14-3-3 protein overexpression reduced the budding of VLPs. Using (33)P labeling, phosphorylated M protein was detected in PIV5-infected cells, and this phosphorylation was nearly absent in cells infected with a recombinant virus harboring an S369A mutation within the M protein. Assembly of the M protein into clusters and filaments at infected cell surfaces was enhanced in cells infected with a recombinant virus defective in 14-3-3 binding. These findings support a model in which a portion of M protein within PIV5-infected cells is phosphorylated at residue S369, binds the 14-3-3 protein, and is held away from sites of virus budding.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism*
  • Amino Acid Sequence
  • Cell Line
  • Down-Regulation*
  • Humans
  • Molecular Sequence Data
  • Parainfluenza Virus 5 / chemistry
  • Parainfluenza Virus 5 / genetics
  • Parainfluenza Virus 5 / physiology*
  • Phosphorylation
  • Protein Binding
  • Rubulavirus Infections / genetics
  • Rubulavirus Infections / metabolism*
  • Rubulavirus Infections / virology
  • Sequence Alignment
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*
  • Virion / chemistry
  • Virion / genetics
  • Virion / physiology*
  • Virus Assembly*


  • 14-3-3 Proteins
  • Viral Matrix Proteins
  • YWHAB protein, human