Journal
EMBO REPORTS
Volume 18, Issue 10, Pages 1740-1751Publisher
WILEY
DOI: 10.15252/embr.201744100
Keywords
amphipathic helix; fusion; IFITM; restriction factor; virus
Categories
Funding
- NIH [AI130110]
- Ohio State University Systems and Integrative Biology Training Program - NIH [GM068412]
- Ohio State University Presidential Fellowship
- Howard Hughes Medical Institute
- CHIKV-Viro-Immuno project [ANR-14-CE14-0015-01]
- TIMTAMDEN project [ANR-14-CE14-0029]
- Labex IBEID program [ANR-10-IHUB-0002]
- ANRS
- Institut Pasteur
Ask authors/readers for more resources
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3-dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections. The homologous amphipathic helix within IFITM1 is also required for the inhibition of infection, indicating that IFITM proteins possess a conserved mechanism of antiviral action. We further demonstrate that the amphipathic helix of IFITM3 is required to block influenza virus hemagglutinin-mediated membrane fusion. Overall, our results provide evidence that IFITM proteins utilize an amphipathic helix for inhibiting virus fusion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available