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 | |
| State | Published - Sep 2010 |
Funding
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.
Keywords
- Cellbio
- Humdisease
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
