title: Influenza virus M2 protein mediates ESCRT-independent membrane scission.
abstract: Many 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.
authors.affiliation: Department of Biochemistry, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Rossman
authors.forename: Xianghong
authors.initials: X
authors.lastname: Jing
authors.forename: George P
authors.initials: GP
authors.lastname: Leser
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism* / Q000648:ultrastructure; D008563:Membrane Lipids / Q000378:metabolism; D008854:Microscopy, Electron; D017434:Protein Structure, Tertiary; D014763:Viral Matrix Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D057074:Virus Release; D000086082:Viroporin Proteins
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D008563:Membrane Lipids; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins