Transmembrane domain of IFITM3 is responsible for its interaction with influenza virus HA2 subunit

Wang Xu1, Yuhang Wang2, Letian Li3

  • 1College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China.

Virologica Sinica
|July 9, 2022
PubMed

Insights

Interferon-inducible transmembrane protein 3 (IFITM3) directly interacts with the HA2 subunit of influenza hemagglutinin, blocking viral entry. This interaction, mediated by transmembrane domains, offers new insights into IFITM3

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Interferon-inducible transmembrane protein 3 (IFITM3) is known to restrict influenza virus infection.
  • The precise mechanism by which IFITM3 inhibits viral membrane fusion and entry remains unclear.

Purpose of the Study:

  • To investigate the function and critical region of IFITM3 in blocking influenza virus entry mediated by hemagglutinin (HA).
  • To elucidate the molecular interaction between IFITM3 and influenza HA.

Main Methods:

  • Utilized pseudoviruses harboring HA proteins from H5 and H7 influenza viruses to confirm IFITM3 restriction.
  • Performed subcellular co-localization and immunoprecipitation assays to analyze IFITM3-HA interactions.
  • Conducted truncated analyses to identify key interacting domains.

Main Results:

  • IFITM3 was confirmed to restrict HA-mediated entry of H5 and H7 influenza viruses.
  • IFITM3 directly interacts with the HA2 subunit, but not the HA1 subunit, of influenza HA.
  • The transmembrane domains of both IFITM3 and HA2 are crucial for their interaction, which extends to other influenza A and B subtypes.

Conclusions:

  • Demonstrated a direct interaction between IFITM3 and influenza HA via the transmembrane domain.
  • This finding provides a novel perspective on the mechanism of IFITM3-mediated restriction of influenza virus infection.
  • Highlights the significance of the IFITM3-HA2 interaction in viral entry and potential therapeutic targets.