IFITM3 Restricts Human Metapneumovirus Infection

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Human metapneumovirus (hMPV) employs a dual cellular entry mechanism, involving either plasma membrane fusion or endosomal fusion.
• Cellular factors influencing hMPV entry pathways remain largely uncharacterized.

Purpose of the Study:

• To investigate the role of interferon-induced transmembrane protein 3 (IFITM3) in restricting hMPV infection.
• To elucidate the mechanism by which IFITM3 affects hMPV cellular entry.

Main Methods:

• Assessed IFITM3's impact on hMPV infection levels.
• Examined the effect of an IFITM3 variant with altered localization.
• Investigated the role of the F protein in IFITM3-mediated restriction.
• Tested the influence of amphotericin B on IFITM3-inhibited infection.
• Evaluated the interplay between IFITM3 and toll-like receptor 7 (TLR7) in hMPV entry.

Main Results:

• IFITM3 significantly inhibits hMPV infection, comparable to endocytosis inhibitors.
• An IFITM3 variant localized to the plasma membrane enhanced viral restriction.
• IFITM3 blocks hMPV F protein-mediated membrane fusion, an effect reversible by amphotericin B.
• Toll-like receptor 7 (TLR7) enhances infection by certain hMPV strains, but IFITM3 still restricts infection in TLR7-expressing cells.

Conclusions:

• IFITM3 functions as an endosomal restriction factor against hMPV.
• IFITM3's antiviral activity is mediated by inhibiting viral fusion at the endosome.
• Understanding IFITM3's role provides insights into host-pathogen interactions and potential therapeutic targets for hMPV.