IFITM3 requires an amphipathic helix for antiviral activity

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Nicholas M Chesarino1, Alex A Compton2,3,4, Temet M McMichael1

  • 1Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.

EMBO Reports
|August 25, 2017
PubMed

Insights

Interferon-induced transmembrane protein 3 (IFITM3) uses a specific helix to block viruses from entering cells. This amphipathic helix is crucial for IFITM3

Area of Science:

  • Virology and Molecular Biology
  • Cellular and Membrane Biology
  • Bioinformatics and Structural Biology

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is a key cellular antiviral factor.
  • IFITM3's mechanism for blocking virus-cell membrane fusion remains incompletely understood.
  • Previous research suggested IFITM3 functions within transmembrane domains.

Purpose of the Study:

  • To elucidate the precise mechanism by which IFITM3 inhibits viral entry.
  • To identify structural elements within IFITM3 critical for its antiviral activity.
  • To determine if this mechanism is conserved across different IFITM proteins.

Main Methods:

  • Bioinformatic analysis to predict IFITM3 secondary structures.
  • Identification and characterization of a conserved amphipathic helix.
  • Functional assays using various viruses (influenza, Zika, VSV, Ebola, HIV) to assess antiviral inhibition.

Main Results:

  • A conserved, short amphipathic helix was identified in a previously assumed transmembrane region of IFITM3.
  • This amphipathic helix is essential for IFITM3's broad-spectrum antiviral activity against multiple viruses.
  • The homologous helix in IFITM1 is also required for antiviral function, suggesting a conserved mechanism.

Conclusions:

  • IFITM proteins, including IFITM3, employ a conserved amphipathic helix mechanism to inhibit virus fusion.
  • This helix directly interferes with viral hemagglutinin-mediated membrane fusion.
  • The findings reveal a novel structural basis for IFITM-mediated antiviral defense.
Keywords:
IFITMamphipathic helixfusionrestriction factorvirus

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