Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission

Jeremy S. Rossman; Xianghong Jing; George P. Leser; Robert A. Lamb

doi:10.1016/j.cell.2010.08.029

Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission

Jeremy S. Rossman, Xianghong Jing, George P. Leser, Robert A. Lamb^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

318 Scopus citations

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. PaperClip:

Original language	English (US)
Pages (from-to)	902-913
Number of pages	12
Journal	Cell
Volume	142
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2010.08.029
State	Published - Sep 2010

Keywords

Cellbio
Humdisease

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2010.08.029

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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. PaperClip:",

keywords = "Cellbio, Humdisease",

author = "Rossman, {Jeremy S.} and Xianghong Jing and Leser, {George P.} and Lamb, {Robert A.}",

note = "Funding Information: We thank members of the Lamb laboratory for helpful discussions and critical reading of the manuscript. The electron microscopy was performed in the Northwestern University Biological Imaging Facility. This research was supported in part by a grant R01 AI-20201 from the National Institute of Allergy and Infectious Diseases. J.S.R. is an Associate and R.A.L. is an Investigator of the Howard Hughes Medical Institute. ",

year = "2010",

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doi = "10.1016/j.cell.2010.08.029",

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AU - Jing, Xianghong

AU - Leser, George P.

AU - Lamb, Robert A.

N1 - Funding Information: We thank members of the Lamb laboratory for helpful discussions and critical reading of the manuscript. The electron microscopy was performed in the Northwestern University Biological Imaging Facility. This research was supported in part by a grant R01 AI-20201 from the National Institute of Allergy and Infectious Diseases. J.S.R. is an Associate and R.A.L. is an Investigator of the Howard Hughes Medical Institute.

PY - 2010/9

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N2 - 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. PaperClip:

AB - 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. PaperClip:

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