Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission

SummaryMany viruses utilize host ESCRT proteins for budding; however, influenza virus budding is thought to be ESCRT-independent. In this study we have found a role for the influenza virus M2 proton-selective ion channel protein in mediating virus budding. We observed that a highly conserved amphipathic helix located within the M2 cytoplasmic tail mediates a cholesterol-dependent alteration in membrane curvature. The 17 amino acid amphipathic helix is sufficient for budding into giant unilamellar vesicles, and mutation of this sequence inhibited budding of transfected M2 protein in vivo. We show that M2 localizes to the neck of budding virions and that mutation of the M2 amphipathic helix results in failure of the virus to undergo membrane scission and virion release. These data suggest that M2 mediates the final steps of budding for influenza viruses, bypassing the need for host ESCRT proteins.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (3259 K)

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (196 K)Download as PowerPoint slideHighlights► The influenza virus M2 protein contains a highly-conserved amphipathic helix ► The M2 amphipathic helix is sufficient for ESCRT-independent budding in vitro ► M2 localizes to the neck of budding virions ► Mutation of the M2 amphipathic helix inhibits membrane scission and virion release