IFITM3 requires an amphipathic helix for antiviral activity

Author:

Chesarino, Nicholas M

Compton, Alex [ORCID]

McMichael, Temet M

Kenney, Adam D

Zhang, Lizhi

Soewarna, Victoria

Davis, Matthew

Schwartz, Olivier [ORCID]

Yount, Jacob S [ORCID]
Author Address

Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA., Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France., CNRS URA 3015, Paris, France., HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA yount.37@osu.edu.,

Abstract:

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. © 2017 The Authors.

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