F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is critical for efficient influenza virus budding

Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4615-20. doi: 10.1073/pnas.1114728109. Epub 2012 Mar 5.


The identification of host factors involved in virus replication is important to understand virus life cycles better. Accordingly, we sought host factors that interact with the influenza viral nonstructural protein 2 by using coimmunoprecipitation followed by mass spectrometry. Among proteins associating with nonstructural protein 2, we focused on the β subunit of the F1Fo-ATPase, which received a high probability score in our mass spectrometry analysis. The siRNA-mediated down-regulation of the β subunit of the F1Fo-ATPase reduced influenza virion formation and virus growth in cell culture. We further found that efficient influenza virion formation requires the ATPase activity of F1Fo-ATPase and that plasma membrane-associated, but not mitochondrial, F1Fo-ATPase is important for influenza virion formation and budding. Hence, our data identify plasma membrane-associated F1Fo-ATPase as a critical host factor for efficient influenza virus replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism*
  • HEK293 Cells
  • Humans
  • Influenza, Human / virology
  • Mass Spectrometry / methods
  • Models, Biological
  • Models, Statistical
  • Orthomyxoviridae / metabolism*
  • Plasmids / metabolism
  • Proteomics / methods
  • Proton-Translocating ATPases / chemistry*
  • Proton-Translocating ATPases / metabolism
  • RNA, Small Interfering / metabolism
  • Viral Nonstructural Proteins / chemistry*
  • Virus Release*
  • Virus Replication


  • RNA, Small Interfering
  • Viral Nonstructural Proteins
  • Proton-Translocating ATPases